Oncology Research 26(8) Abstracts

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Oncology Research, Vol. 26, pp. 1143-1154, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14965095236521
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells In Vitro and In Vivo via Targeting miR-203

Shilei Wang,* Yuzuo Hui,* Xiaoming Li,and Qingbin Jia*

*Department of Neurosurgery, Liaocheng People’s Hospital, Shandong, P.R. China
†Department of Pharmacy, Liaocheng People’s Hospital, Shandong, P.R. China

Gliomas are the most common primary brain tumors with high mortality. The treatment for gliomas is largely limited due to its uncomprehending pathological mechanism. Here we aimed to investigate the effect of long noncoding RNA (lncRNA) coiled-coil domain-containing 26 (CCDC26) in glioma progression. In our study, the expression of CCDC26 was found upregulated in glioma tissues and cell lines compared with normal tissues and cell lines. Further exploration detected decreased cell proliferation and increased cell apoptosis in U-251 and M059J cells transfected with CCDC26-siRNA. In addition, the silencing of CCDC26 strongly reduced the wound closing rate and the number of invasive cells compared with the scramble group. Simultaneously, the expression of miR-203 was found suppressed in glioma tissues and cells lines. Suppressed level of miR-203 was then elevated in U-251 and M059J cells transfected with CCDC26-siRNA. The result of the luciferase activity assay also showed that the luciferase activity was strongly strengthened by adding the miR-203 inhibitor into the CCDC26 WT group. Moreover, CDCC26-siRNA counteracted the effect of the miR-203 inhibitor in facilitating cell viability and mobility in U-251 cells. The in vivo experiment also revealed that CCDC26-siRNA inhibited glioma growth and metastasis. Taken together, our research indicated a CCDC26/miR-203 pathway in regulating the growth and metastasis of gliomas, providing new viewpoints and promising targets for glioma therapy.

Key words: Coiled-coil domain-containing 26 (CCDC26); miR-203; Growth; Migration; Glioma

Address correspondence to Qingbin Jia, Department of Neurosurgery, Liaocheng People’s Hospital, No. 67 Dongchang Road, Dongchangfu District, Liaocheng, Shandong 252000, P.R. China. Tel: 86-15964360717; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1155-1165, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15041934685237
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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miR-203 Suppresses Bladder Cancer Cell Growth and Targets Twist1

Jie Shen,* Jianhua Zhang,† Minhui Xiao,* Junfeng Yang,* and Ningnan Zhang*

*Department of Urology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, P.R. China
†Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China

miR-203 is an epigenetically silenced tumor-suppressive microRNA in tumors. This study was designed to investigate the effects of miR-203 on the proliferation, migration, invasion, and apoptosis of bladder cancer (BCa) cells. The expression levels of miR-203 in BCa tissues, normal adjacent tissues, and BCa cell lines were detected. BCa cells were transfected with miR-203 mimic and inhibitor to investigate the effect of miR-203 on cell functions and the epithelial–mesenchymal transition (EMT). Cotransfection with miR-203 inhibitor and shRNA of the predicted target gene Twist1 (si-Twist1) was performed to investigate the target relationship of miR-203 and Twist1. The effects of knockdown of Twist1 on cell functions were also investigated. The expression of miR-203 was significantly reduced in BCa tissues and cells, in comparison with the control. miR-203 mimic significantly reduced cell viability, invasion, migration, and EMT, and enhanced cell apoptosis. On the contrary, miR-203 inhibitor showed the opposite results. However, the administration of si-Twist1 cancelled the effect of miR-203 inhibitor on cell proliferation, apoptosis, invasion, and migration. These demonstrated that miR-203 may function as a tumor-suppressive microRNA in BCa by negatively targeting Twist1. Both Twist1 and miR-203 might be explored as potential targets for studying the mechanism related to BCa pathogenesis and therapy.

Key words: miR-203; Bladder cancer (BCa); Proliferation; Invasion

Address correspondence to Jianhua Zhang, Department of Urology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua District, Kunming, Yunnan 650032, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1167-1174, 2018
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DOI: https://doi.org/10.3727/096504017X
15051741798389
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-1290 Contributes to Colorectal Cancer Cell Proliferation by Targeting INPP4B

Qingzhu Ma,* Yan Wang,† Hualing Zhang,* and Fengqiang Wang†

*Department of Gastroenterology, Liaocheng People’s Hospital, Liaocheng, P.R. China
†Department of Respiratory Medicine, Liaocheng People’s Hospital, Liaocheng, P.R. China

Colorectal cancer (CRC) is one of the most common oncological conditions worldwide, to date. MicroRNA-1290 (miR-1290) has been demonstrated to regulate its progression. We studied the role of miR-1290 in CRC progression. The gene was upregulated in CRC tissues and cells. Its overexpression promoted CRC cell proliferation analyzed by MTT assay, colony formation assay, and soft agar growth assay. In addition, miR-1290 knockdown inhibited CRC cell proliferation. We also found that miR-1290 overexpression reduced the p27 level and increased cyclin D1 at both the mRNA and protein levels, whereas miR-1290 knockdown increased p27 and reduced cyclin D1, confirming miR-1290 promoted CRC cell proliferation. Inositol polyphosphate 4-phosphatase B (INPP4B) was the target of miR-1290. Luciferase reporter assay revealed that miR-1290 directly bound to the 3
¢-UTR of INPP4B; the mutated seed sites in miR-1290 abrogated this effect. Double knockdown of INPP4B and miR-1290 promoted CRC cell proliferation, suggesting miR-1290 promoted CRC cell proliferation by targeting INPP4B.

Key words: miR-1290; INPP4B; Colorectal cancer (CRC); Cell proliferation

Address correspondence to Qingzhu Ma, Department of Gastroenterology, Liaocheng People’s Hospital, 67 Dongchang West Road Liaocheng, 252000, P.R. China. Tel:+86-0635-8276289; Fax:+86-0635-8276289; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1175-1182, 2018
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DOI: https://doi.org/10.3727/096504018X
15149761920868
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells

Hung-Tsung Lee,* Cheng-Hsieh Huang,† Wuan-Chun Chen,† Chi-Shan Tsai,† Yu-Lin Chao,† Szu-Han Liu,† Jun-Hong Chen,† Yi-Ying Wu,‡ and Yi-Ju Lee†§

*Division of Pulmonary Medicine, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan, Republic of China
†Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, Republic of China
‡Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, Republic of China
§Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China

Lung cancer is the leading cause of cancer deaths worldwide. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. Transglutaminase 2 (TG2), belonging to the transglutaminase superfamily, is a versatile protein with enzymatic and nonenzymatic functions. It mainly localizes inside the cell, but also appears extracellularly. Recent findings have demonstrated the involvement of TG2 in cancer development. Here we examine the role of TG2 in metastasis of lung cancer using a lung cancer cell line CL1-0, which exhibits low invasiveness, and its invasive subline CL1-5. Our results show that CL1-5 cells express a higher amount of TG2 than CL1-0 cells. Overexpression of TG2 in CL1-0 enhances cell migration and invasion, and lowering TG2 expression in CL1-5 cells reduces their ability to do so. The transamidase activity of TG2 is not required since cells expressing the inactive TG2 mutant or treated with a TG2 inhibitor are still able to migrate and invade. TG2-stimulated migration and invasion are, at least in part, mediated by Rac, as inhibition of Rac activity suppresses cell migration and invasion. Lastly, exogenous application of recombinant TG2 protein to CL1-0 cells substantially augments cell migration and invasion, suggesting the significance of extracellular TG2 in promoting these events. Collectively, our results show that TG2 plays a positive role in cell migration and invasion, and this might help metastasis of lung cancer cells.

Key words: Transglutaminase 2 (TG2); Lung cancer; Migration; Invasion; Rac

Address correspondence to Yi-Ju Lee, Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan, Republic of China. Tel: +886-4-2473-0022, ext. 11702; Fax: +886-4-2324-8172; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1183-1189, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15151495109394
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-338-3p Suppresses Proliferation of Human Liver Cancer Cells by Targeting SphK2

Geqiong Xiao,* Qiong Wang,* Bo Li,† Xiaohui Wu,‡ Hui Liao,* Yili Ren,* and Ning Ai†*

*Department of Oncology, ShaoXing Municipal Hospital, Shaoxing, Zhejiang, P.R. China
†Department of Interventional Radiology, The 4th Hospital of Hebei Medical University, Shi Jiazhuang, Hebei, P.R. China
‡Department of Hepatobiliary Surgery, The 4th Hospital of Hebei Medical University, Shi Jiazhuang, Hebei, P.R. China

Recent studies have revealed abnormal expression of miRNAs in various tumors. Although microRNA-338-3p (miR-338-3p) plays an important role in many types of tumors, its influence on liver cancer (LC) is unknown. In this study, we found that expression of miR-338-3p was decreased in LC cells and tissues. Colony formation and cell proliferation were suppressed by enhanced expression of miR-338-3p in LC cells. Moreover, miR-338-3p targeted sphingosine kinase 2 (SphK2). Silencing of SphK2 had an identical influence as overexpression of miR-338-3p in LC cells. Overexpression of SphK2 without the 3
-untranslated region remarkably enhanced the growth suppression triggered by miR-338-3p in LC cells. These findings indicate that miR-338-3p influences the development of LC by targeting SphK2, suggesting that miR-338-3p can be targeted as an innovative therapeutic strategy for LC.

Key words: Liver cancer (LC); Proliferation; MicroRNA-338-3p; Sphingosine kinase 2 (SphK2)

Address correspondence to Ning Ai, Department of Interventional Radiology, The 4th Hospital of Hebei Medical University, #12 Jian Kang Road, Shi Jiazhuang, Hebei 050011, P.R. China. Tel: +86-0311-13803365908; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1191-1200, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15166204902353
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-135a Confers Resistance to Gefitinib in Non-Small Cell Lung Cancer Cells by Upregulation of RAC1

Tingting Zhang*1 and Ning Wang†1

*Department of Oncology, Shengli Oilfield Central Hospital, Dongying, Shandong, P.R. China
†Department of Thoracic Surgery, Shengli Oilfield Central Hospital, Dongying, Shandong, P.R. China

The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small cell lung cancer (NSCLC). However, the therapeutic efficacy of gefitinib is known to be impeded by mutations of EGFR. The aim of the present study was to reveal the role of miR-135a in gefitinib resistance of NSCLC cells. Human NSCLC cell lines, NCI-H1650 and NCI-H1975, were transfected with miR-135a mimic/inhibitor or miR-135a inhibitor plus pEX-RAC1 (a RAC1-expressing vector). The effects of miR-135a and RAC1 expression on cell viability, apoptosis, migration, and invasion were then detected. The transfected cells were exposed to 0–20 μM gefitinib, and cell viability was then detected at 48 h posttreatment. Western blot analysis was performed to detect the expression changes of main factors in the PI3K/AKT pathway. miR-135a overexpression promoted viability, migration, and invasion, but inhibited apoptosis of NCI-H1650 and NCI-H1975 cells. Cell viability was significantly reduced by gefitinib, and the LC
50 values of gefitinib in NCI-H1650 and NCI-H1795 cells were 0.845 and 0.667 μM, respectively. miR-135a overexpression could increase cell viability even under high concentrations of gefitinib. Rac1 was not predicted as a target of miR-135a, while miR-135a could upregulate the expression of RAC1. miR-135a promoted cell growth and metastasis and activated the PI3K/AKT signaling pathway via a RAC1-dependent manner. To conclude, this study demonstrated that miR-135a confers NSCLC cell resistance to gefitinib via upregulation of RAC1. Therapies designed to downregulate miR-135a may help NSCLC patients to overcome gefitinib resistance.

Key words: miR-135a; Drug resistance; Gefitinib; Non-small cell lung cancer (NSCLC); RAC1; PI3K/AKT signaling pathway

1These authors provided equal contribution to this work.
Address correspondence to Ning Wang, Department of Thoracic Surgery, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying 257000, Shandong, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1201-1205, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15154104709325
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90

Bui Thi Kim Ly* and Hoang Thanh Chi†‡

*Department of Food Biotechnology, Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City, Vietnam
†Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam
‡Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam

FMS-like tyrosine kinase-3 fragments from exon 14 to the end without any mutations or deletions have been reported to fuse to ETV6 (TEL) in a few cases of myeloid/lymphoid neoplasms with eosinophilia carrying a translocation t(12;13)(p13;q12). This fusion protein confers constitutive activation on the FLT3 fragment and induces factor-independent growth in transfected Ba/F3 cells, indicating that it is an oncoprotein. However, the mechanism controlling the stability of this oncoprotein is unknown. In this study, we focus on finding factors controlling the stability of ETV6/FLT3. We have shown that the stability of ETV6/FLT3 is regulated by the Hsp90 chaperone. ETV6/FLT3 fusion protein forms a complex with Hsp90 by coimmunoprecipitation analyses using an Hsp90 antibody. The association between ETV6/FLT3 fusion protein and Hsp90 was impaired after treating ETV6/FLT3 transient transfection cos7 cells with 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG induced a time- and dose-dependent downregulation of ectopically expressed ETV6/FLT3 protein in cos7 and HeLa-transfected cells. By using cycloheximide to block new protein translation, we found that 17-AAG accelerated the decay of ETV6/FLT3. Our findings could contribute to more understanding of the ETV6/FLT3 regulation through Hsp90 chaperone and open the way to finding effective treatment strategies for this rare disease.

Key words: ETS-translocation variant 6 (ETV6)/FMS-like tyrosine kinase-3 (FLT3); Tel/FLT3; Heat shock protein 90 (Hsp90)

Address correspondence to Hoang Thanh Chi, Department for Management of Science and Technology Development, Faculty of Applied Sciences, Ton Duc Thang University, 19 Nguyen Huu Tho Street, Tan Phong Ward, District 7, Ho Chi Minh City, Vietnam. Tel: (84-8) 37755058; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1207-1213, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15046134836575
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Swainsonine
Inhibits Invasion and the EMT Process in Esophageal Carcinoma Cells by Targeting Twist1

Junxun Ma, Lijie Wang, Jinyu Li, Guoqing Zhang, Haitao Tao, Xiaoyan Li, Danyang Sun, and Yi Hu

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, P.R. China

Esophageal cancer is a common gastrointestinal cancer, with a very high mortality rate in patients with metastasis. Swainsonine, a cytotoxic fungal alkaloid, has been shown to inhibit cell growth in esophageal cancer. In the present study, we explored the effects of swainsonine on cell invasion and metastasis in esophageal cancer cells. Human esophageal carcinoma cells were treated with different doses of swainsonine, and then cell viability, invasion, and apoptosis were measured. The mRNA and protein expressions of Twist1, apoptosis- and EMT-related factors, and PI3K/AKT pathway factors were detected by qRT-PCR and Western blot. Swainsonine had no effect on esophageal cancer cell viability and apoptosis, but it significantly decreased cell invasion in a dose-dependent manner. Swainsonine increased the expression of E-cadherin but decreased the expression of N-cadherin, vimentin, ZEB1, and snail in a dose-dependent manner, thereby inhibiting EMT. Last, we found that swainsonine inhibits cell invasion and EMT in the esophageal carcinoma cells by downregulation of Twist1 and deactivation of the PI3K/AKT signaling pathway.

Key words: Swainsonine; Esophageal carcinoma; Cell invasion; Metastasis; Epithelial–mesenchymal transition (EMT); Twist1

Address correspondence to Yi Hu, Department of Medical Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1215-1225, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15021536183526
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Upregulation of MicroRNA-4262 Targets Kaiso (ZBTB33) to Inhibit the Proliferation and EMT of Cervical Cancer Cells

Jing Feng

Department of Gynecology, Cangzhou Central Hospital, Hebei, P.R. China

More and more studies have reported that dysregulation of microRNAs (miRNAs) leads to the proliferation and EMT of multiple cancers. Recently, several reports have demonstrated that dysregulation of miR-4262 occurs in numerous cancers. However, its role and precise mechanism in human cervical cancer (CC) have not been well clarified. Hence, this study aimed to explore the biological roles and precise mechanisms of miR-4262 in CC cell lines. The level of miR-4262 was found to be significantly decreased in CC tissues and cell lines. Moreover, decreased expression of miR-4262 was closely related to increased expression of Kaiso (ZBTB33), which belongs to the BTB/POZ family, in CC tissues and cell lines. The proliferation and EMT of CC cells were inhibited by a miR-4262 mimic. However, downregulation of miR-4262 enhanced the proliferation and EMT of CC cells. Next, bioinformatics analysis predicted that miR-4262 might directly target the Kaiso gene. Besides, luciferase reporter assay had confirmed this result. Moreover, introduction of Kaiso in CC cells partially blocked the effects of miR-4262 mimic. In conclusion, miR-4262 suppressed the proliferation and EMT of CC cells by directly downregulating Kaiso.

Key words: Cervical cancer (CC); Proliferation; Epithelial–mesenchymal transition (EMT); MicroRNA-4262; Kaiso

Address correspondence to Dr. Jing Feng, Department of Gynecology, Cangzhou Central Hospital, No. 16 Xinhua Road, Hebei 061000, P.R. China. Tel: +86-0317-2075532; Fax: +86-0317-2075532; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1227-1234, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15178736525106
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Puerarin
Inhibits Proliferation and Induces Apoptosis by Upregulation of miR-16 in Bladder Cancer Cell Line T24

Xiaoyun Liu,1 Shuguang Li,1 Yanyan Li, Bo Cheng, Bo Tan, and Gang Wang

Department of Urology, Shengli Oilfield Central Hospital, Dongying, Shandong, P.R. China

Bladder cancer (BC) is a common disease of the urinary system. Puerarin is a flavonoid extracted from
Pueraria lobata. However, the role of puerarin in BC remains unclear. Hence, this study aimed to investigate the effect of puerarin on BC cells. Cell viability, proliferation, and apoptosis were measured by CCK-8, BrdU assay, and flow cytometry analysis, respectively. The expressions of miR-16, apoptosis-related factors, and the main factors of the NF-κB pathway were analyzed by qRT-PCR and Western blot. In this study, we found that cell viability and proliferation were significantly reduced, cell apoptosis was enhanced, and the mRNA level of miR-16 was upregulated in puerarin-treated T24 cells. Further, silencing of miR-16 inhibited the decrease in cell viability and the increase in apoptosis. The expression of main factors involved in the NF-κB signaling pathway was downregulated in the puerarin group, while miR-16 silencing alleviated these downregulations. More importantly, puerarin deactivated the NF-κB signaling pathway via upregulation of miR-16. Also, miR-16 downregulated COX-2 expression via deactivation of the NF-κB signaling pathway. This study demonstrated that puerarin could inhibit cell proliferation, promote cell apoptosis, and deactivate NF-κB signaling pathway via upregulation of miR-16 in T24 cells.

Key words: Puerarin; MicroRNA-16 (miR-16); Bladder cancer; Cyclooxygenase 2 (COX-2); Nuclear factor κ light chain enhancer of activated B cells (NF-κB) signaling pathway

1These authors provided equal contribution to this work.
Address correspondence to Shuguang Li, Department of Urology, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying 257034, Shandong, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1235-1243, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15179661552702
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Triptolide
Inhibits Proliferation and Migration of Human Neuroblastoma SH-SY5Y Cells by Upregulating MicroRNA-181a

Jian Jiang,* Xuewen Song,† Jing Yang,* Ke Lei,* Yongan Ni,* Fei Zhou,‡ and Lirong Sun*

*Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China
†Outpatient Department, Qingdao No. 1 Sanitarium, Qingdao, Shandong, P.R. China
‡Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China

Neuroblastoma is the primary cause of cancer-related death for children 1 to 5 years of age. New therapeutic strategies and medicines are urgently needed. This study aimed to investigate the effects of triptolide (TPL), the major active component purified from
Tripterygium wilfordii Hook F, on neuroblastoma SH-SY5Y cell proliferation, migration, and apoptosis, as well as underlying potential mechanisms. We found that TPL inhibited SH-SY5Y cell viability, proliferation, and migration, but induced cell apoptosis. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 after TPL treatment in SH-SY5Y cells was decreased. The expression of microRNA-181a (miR-181a) was upregulated after TPL treatment. Moreover, suppression of miR-181a reversed the effects of TPL on SH-SY5Y cell proliferation, apoptosis, and migration. Overexpression of miR-181a enhanced the TPL-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor κ light chain enhancer of activated B cells (NF-κB) pathways. In conclusion, our research verified that TPL inhibited the proliferation and migration of human neuroblastoma SH-SY5Y cells by upregulating the expression of miR-181a.

Key words: Triptolide; MicroRNA-181a; Neuroblastoma; Cell apoptosis; p38MAPK signaling pathway; NF-κB signaling pathway

Address correspondence to Lirong Sun, Department of Pediatrics, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Huangdao District, Qingdao 266555, Shandong, P.R. China. Tel: +86-0532-82911847; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1245-1255, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14944585873668
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA CRNDE/PRC2 Participated in the Radiotherapy Resistance of Human Lung Adenocarcinoma Through Targeting p21 Expression

Ming Zhang,* Change Gao,† Yi Yang,* Gaofeng Li,‡ Jian Dong,§ Yiqin Ai,* Nan Chen,‡ and Wenhui Li*

*Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, P.R. China
†Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China
‡Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, P.R. China
§The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, P.R. China

Long noncoding RNAs (lncRNAs), a new class of functional regulators involved in human tumorigenesis, have been attracting the increasing attention of researchers. The lncRNA colorectal neoplasia differentially expressed (CRNDE) gene, transcribed from chromosome 16 on the strand opposite the adjacent IRX5 gene, was originally found to be increased in CRC and was reported to be abnormally expressed in many cancers. However, its potential role and the molecular mechanism underlying the radioresistant phenotype formation of lung adenocarcinoma (LAD) remain unclear. In our present study, we identified that CRNDE was significantly upregulated in LAD tissue and radioresistant LAD cell lines. A high level of CRNDE expression was significantly correlated with poor differentiation, TNM stage, lymph node metastasis, radiotherapy response, and a significantly shorter overall survival. Gain- and loss-of-function tests revealed that CRNDE could influence the radiosensitivity of LAD cells by affecting the G1/S transition and causing apoptosis of LAD cells in vitro. Additionally, the mechanistic investigations showed that CRNDE could interact with PRC2 and recruit its core component EZH2 to p21 (CDKN1A) promoter regions and repress its transcription. Furthermore, rescue experiments were performed to confirm that CRNDE oncogenic function was partly through regulating p21. In conclusion, our data suggest that CRNDE may function as an oncogene by modulating p21, finally contributing to the radioresistant phenotype formation of LAD cells.

Key words: Long noncoding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE); Polycomb-repressive complex 2 (PRC2); p21; Lung adenocarcinoma (LAD); Radioresistant

Address correspondence to Wenhui Li, Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province 650118, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1257-1265, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15172756878992
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA FGFR3-AS1 Promotes Hepatocellular Carcinoma Carcinogenesis via Modulating the PI3K/AKT Pathway

Juhua Zhuang,*1 Saifei He,*1 Guoyu Wang,* Guangdong Wang,*† Jing Ni,* Suiliang Zhang,‡ Ying Ye,* and Wei Xia*

*Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
†Department of Research and Development, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
‡Oncology Department, the Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

Hepatocellular carcinoma (HCC) as one of the most refractory cancers leads to high mortality worldwide. Long noncoding RNAs have been widely acknowledged as important biomarkers and therapeutic targets in HCC. In this study, we investigated the effects of long noncoding RNA FGFR3-AS1 on tumor growth and metastasis in HCC. First, we found that the expression of FGFR3-AS1 was upregulated about threefold in HCC samples and cell lines. We knocked down FGFR3-AS1 in Huh7 and Hep3B cells and found that FGFR3-AS1 knockdown significantly inhibited cell proliferation but induced apoptosis. Moreover, FGFR3-AS1 knockdown led to more HCC cells arrested in the G0
stage. FGFR3-AS1 knockdown significantly inhibited cell migration and invasion. Additionally, we found that FGFR3-AS1 silencing dramatically delayed tumor growth in vivo. We found that, mechanistically, FGFR3-AS1 silencing decreased the activation of the PI3K/AKT signaling pathway. Taken together, our data demonstrated the pro-oncogenic role of FGFR3-AS1 in HCC and suggested that FGFR3-AS1 may serve as a novel biomarker for the diagnosis and therapeutic target for HCC treatment.

Key words: Hepatocellular carcinoma (HCC); FGFR3-AS1; Proliferation; Migration; PI3K/AKT

1These authors provided equal contribution to this work.
Address correspondence to Professor Wei Xia, Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai Lun Road, Shanghai 201203, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Professor Ying Ye, Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, No. 1200, Cai Lun Road, Shanghai 201203, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1267-1274, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15172227703244
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

B7-Homolog 4 Promotes Epithelial–Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB

Haoran Wu,1 Xugang Wang,1 Naixin Mo, Liang Zhang, Xiaoliang Yuan, and Zhong

Department of Urology, Wujin Hospital, Affiliated to Jiangsu University, Changzhou, P.R. China

B7-homolog 4 (B7-H4), a member of the B7 family of costimulatory molecules, has been reported to be upregulated in urothelial cell carcinoma. This study was conducted to explore the biological role of B7-H4 in the aggressiveness of bladder cancer and the associated molecular mechanism. We found that the mRNA and protein levels of B7-H4 were significantly greater in bladder cancer cell lines than in SV-HUC-1 (normal human urothelial cells). Overexpression of B7-H4 significantly promoted bladder cancer cell migration and invasion, whereas knockdown of B7-H4 exerted an opposite effect. However, the growth of bladder cancer cells was not altered by B7-H4 overexpression or knockdown. Overexpression of B7-H4 promoted epithelial–mesenchymal transition (EMT), as evidenced by decreased E-cadherin and increased vimentin expression. The EMT inducers Twist1 and Snail were upregulated by B7-H4 overexpression and downregulated by B7-H4 silencing. Mechanistically, overexpression of B7-H4 induced the activation of NF-
κB signaling. Pharmacological inhibition of NF-κB partially prevented B7-H4-mediated bladder cancer cell invasion. Taken together, B7-H4/NF-κB signaling is involved in the EMT and invasion of bladder cancer cells and represents a new candidate target for the treatment of bladder cancer.

Key words: B7-H4; Bladder cancer; Invasion; NF-κB signaling

1These authors provided equal contribution to this work and should be considered as co-first authors.
Address correspondence to Zhong , Department of Urology, Wujin Hospital, Affiliated to Jiangsu University, No. 2 Yongning North Road, Changzhou 213017, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1275-1283, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15185735627746
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-598 Inhibits Cell Proliferation and Invasion of Glioblastoma by Directly Targeting Metastasis Associated in Colon Cancer-1 (MACC1)

Ning Wang,*1 Yang Zhang,†1 and Huaxin Liang‡

*Department of Neurosurgery, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Hubei, P.R. China
†Department of Anesthesiology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Hubei, P.R. China
‡Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Jilin, P.R. China

The dysregulation of microRNA (miRNA) expression is closely related with tumorigenesis and tumor development in glioblastoma (GBM). In this study, we found that miRNA-598 (miR-598) expression was significantly downregulated in GBM tissues and cell lines. Restoring miR-598 expression inhibited cell proliferation and invasion in GBM. Moreover, we validated that metastasis associated in colon cancer-1 (MACC1) is a novel target of miR-598 in GBM. Restoring MACC1 expression reversed the inhibitory effects of miR-598 overexpression on GBM cells. In addition, miR-598 overexpression suppressed Met/AKT pathway activation in GBM. Our results provided compelling evidence that miR-598 serves tumor-suppressive roles in GBM and that its antioncogenic effects are mediated chiefly through the direct suppression of MACC1 expression and regulation of the Met/AKT signaling pathway. Therefore, miR-598 is a potential target in the treatment of GBM.

Key words: Glioblastoma; MicroRNA-598; Metastasis associated in colon cancer-1 (MACC1); Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Huaxin Liang, Department of Neurosurgery, China-Japan Union Hospital, Jilin University, No. 126 Xiantai Road, Changchun, Jilin 130033, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1285-1294, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15166193231711
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA GAS5 Promotes Proliferation, Migration, and Invasion by Regulation of miR-301a in Esophageal Cancer

Wei Li, Weidong Zhao, Zhaohui Lu, Wen Zhang, and Xuan Yang

Department of Gastroenterology, Shengli Oilfield Central Hospital, Dongying, P.R. China

Long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been revealed to be associated with the progression of various cancers. However, the biological roles of GAS5 in esophageal cancer (EC) remain unclear. We aimed to thoroughly explore the functions of GAS5 in EC. The results showed that GAS5 expression was increased in EC cells (ECA109, TE-1, TE-3, and EC9706) compared to SHEE cells. Knockdown of GAS5 decreased cell viability, migration, and invasion and induced apoptosis in EC9706 cells. Moreover, miR-301a appeared to be directly sponged by GAS5, and miR-301a suppression obviously alleviated the protumor effects of GAS5. Furthermore, miR-301a positively regulated CXCR4 expression, and overexpression of CXCR4 induced apoptosis and abolished the promoting effect of miR-301a inhibition on cell viability, migration, and invasion. Besides, miR-301a blocked Wnt/
β-catenin and NF-κB signaling pathways by regulation of CXCR4. Our results indicated that GAS5 promoted proliferation and metastasis and inhibited apoptosis by regulation of miR-301a in EC. These data contributed to our understanding of the mechanisms of miRNA–lncRNA interaction and provides a novel therapeutic strategy for EC.

Key words: Esophageal cancer (EC); Growth arrest-specific transcript 5 (GAS5); MicroRNA-301a; Chemokine C-X-C motif receptor 4 (CXCR4); Wnt/β-catenin/NF-κB

Address correspondence to Zhaohui Lu, Department of Gastroenterology, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying 257000, P.R. China. Tel: +86-0546-8770042; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1295-1305, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15172747209020
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-204 Inhibits the Growth and Motility of Colorectal Cancer Cells by Downregulation of CXCL8

Feng Shuai,* Bo Wang,† and Shuxiao Dong‡

*Department of Gastroenterology, East Medical District of Linyi People’s Hospital, Linyi, Shandong, P.R. China
†Department of Pediatrics, Chinese Medicine Hospital in Linyi City, Linyi, Shandong, P.R. China
‡Department of Gastrointestinal Surgery, Linyi People’s Hospital, Linyi, Shandong, P.R. China

Among all of the miRNAs, miR-204 has gained considerable attention in the field of cancer research. This study aimed to reveal the detailed functions and the underlying mechanism of miR-204 in colorectal cancer (CRC) cells. The expressions of miR-204 in CRC tumor tissues and cell lines were monitored. Expressions of miR-204 and CXCL8 in Caco-2 and HT-29 cells were altered by transfection, and then cell viability, apoptosis, migration, invasion, EMT-related protein expression, and PI3K/AKT/mTOR pathway protein expression were assessed. We found that miR-204 was expressed at low levels in CRC tumor tissues and cell lines when compared to their normal controls. miR-204 overexpression reduced the viability, migration, and invasion of Caco-2 and HT-29 cells while significantly inducing apoptosis. miR-204 overexpression upregulated E-cadherin expression and downregulated N-cadherin and vimentin expressions. CXCL8 was a target of miR-204, and miR-204 suppression could not increase cell viability, migration, invasion, and EMT procedure when CXCL8 was silenced. Moreover, miR-204 overexpression decreased the phosphorylated levels of PI3K, AKT, and mTOR. The increased phosphorylations of PI3K, AKT, and mTOR, and the upregulation of CXCL8 induced by miR-204 suppression were all abolished by the addition of LY294002 and AZD8055 (inhibitors of PI3K/AKT and mTOR, respectively). To conclude, we demonstrated a tumor-suppressive miRNA in CRC cell lines, miR-204, which is poorly expressed in CRC tissues and cell lines. miR-204 exerted antigrowth, antimigration, anti-invasion, and anti-EMT activities, which might be via deactivating the PI3K/AKT/mTORpathway and repressing CXCL8 expression.

Key words: miR-204; Colorectal cancer (CRC); Chemokine C-X-C motif ligand 8 (CXCL8); Epithelial–mesenchymal transition (EMT); PI3K/AKT/mTOR pathway

Address correspondence to Shuxiao Dong, Department of Gastrointestinal Surgery, Linyi People’s Hospital, No. 27 Jiefang Road, Linyi 276000, Shandong, P.R. China. Tel: +86-0539-8226999; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it