Oncology Research 26(6) Abstracts

Return to Oncology Research>

Oncology Research, Vol. 26, pp. 827-836, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14934840662335
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer

Lulin Zhang, Jun Yao, Wenyao Li, and Ce Zhang

Department of Oncology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan, P.R. China

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whether miR-21 in CAFs would regulate PDAC’s tumor microenvironment and lead to drug resistance remain unknown. In this study, we evaluated the relationship between CAF activation, miR-21 expression, and drug resistance using tumor samples from PDAC patients. We changed the miR-21 expression level in CAFs and tested its roles in regulating the function of CAFs. In addition, we explored the roles of miR-21 in CAFs in the development of PDAC using an animal model. We found that PDAC patients who were resistant to gemcitabine treatment tended to have higher miR-21 expression and more activated CAFs. An in vitro study showed that CAFs with high miR-21 expression had elevated MMP-3, MMP-9, PDGF, and CCL-7 expression and promoted the invasion of PDAC cell lines. miR-21 overexpression also contributed to the activation of CAFs by regulating the PDCD4 gene. The in vivo study showed that upregulating miR-21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment, but downregulating miR-21 in CAFs suppressed desmoplasia and enhanced the effect of gemcitabine. We concluded that miR-21 promoted the activation of CAFs and contributed to the drug resistance of PDAC.

Key words: Pancreatic cancer; Micro-RNA-21; Cancer-associated fibroblasts (CAFs); Drug resistance

Address correspondence to Jun Yao, Department of Oncology, Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, JianxiDistrict, Luoyang 471003, 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. 837-846, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14920318811721
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA XIST Promotes Osteosarcoma Progression by Targeting Ras-Related Protein RAP2B via miR-320b

Gong-Yi Lv, Jun Miao, and Xiao-Lin Zhang

Department of Spinal Surgery, Tianjin Hospital, Tianjin, P.R. China

Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.

Key words: Long noncoding RNAs (lncRNAs); XIST; Osteosarcoma (OS); miR-320b; RAP2B; Invasion

Address correspondence to Xiao-Lin Zhang, Department of Spinal Surgery, Tianjin Hospital, No. 406 Jiefang South Road, Tianjin 300211, P.R. China. Tel: +86-022-28332917; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Oncology Research, Vol. 26, pp. 847-856, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15016337254632
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-154 Inhibits the Growth and Invasion of Gastric Cancer Cells by Targeting DIXDC1/WNT Signaling

Jifu Song, Zhibin Guan, Maojiang Li, Sha Sha, Chao Song, Zhiwei Gao, and Yongli Zhao

Department of Radiotherapy, Qingdao Jiaozhou City Central Hospital, Jiaozhou, Shandong, P.R. China

MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells. Bioinformatics analysis and Dual-Luciferase Reporter Assay data showed that miR-154 directly targeted the 3′-untranslated region of Dishevelled–Axin domain containing 1 (DIXDC1). Real-time quantitative polymerase chain reaction and Western blot analyses showed that miR-154 overexpression inhibited DIXDC1 expression. An inverse correlation of miR-154 and DIXDC1 was also demonstrated in gastric cancer specimens. Overexpression of miR-154 also significantly suppressed the activation of WNT signaling. Moreover, restoration of DIXDC1 expression significantly reversed the inhibitory effect of miR-154 overexpression on the cell proliferation, invasion, and WNT signaling in gastric cancer cells. Overall, these results suggest that miR-154 inhibits gastric cancer cell growth and invasion by targeting DIXDC1 and could serve as a potential therapeutic target for the treatment of gastric cancer.

Key words: Dishevelled–Axin domain containing 1 (DIXDC1); Gastric cancer; miR-154; Wingless-related integration site (WNT)

Address correspondence to Yongli Zhao, Department of Radiotherapy, Qingdao Jiaozhou City Central Hospital, No. 29 Xuzhou Road, Jiaozhou, Shandong 266300, 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. 857-867, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15016337254597
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Knockdown of Long Noncoding RNA LINC00152 Suppresses Cellular Proliferation and Invasion in Glioma Cells by Regulating miR-4775

Zhankun Zhu,* Jinhua Dai,* Yufeng Liao,* Jianbo Ma,* and Wei Zhou†

*Department of Clinical Laboratory, Ningbo No. 2 Hospital, Ningbo, Zhejiang, P.R. China
†Department of Neurosurgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, P.R. China

Long noncoding RNAs (lncRNAs) play an important role in various biological properties of glioma cells. Herein we aimed to elucidate the function and the possible molecular mechanisms of long intergenic noncoding RNA 152 (LINC00152) in glioma cells. Relative expressions of LINC00152, miR-4775, and CDK6 in U-118 MG cells were regulated by transfections. Thereafter, cell viability, migration, invasion, and apoptosis were analyzed by CCK-8, Transwell, and flow cytometry assays. Dual-Luciferase Reporter Assay was conducted to validate the target genes of LINC00152 and miR-4775. Expression of components of the signal pathways were detected by Western blot. The results showed that LINC00152 knockdown significantly suppressed cell viability, migration, and invasion and induced apoptosis in vitro. Additionally, LINC00152 functioned as a molecular sponge for miR-4775, and inhibition of miR-4775 reversed the tumor-suppressive effects of LINC00152 knockdown on glioma cells. Furthermore, CDK6 was confirmed to be a target of miR-4775, and overexpression of CDK6 reduced apoptosis and abolished the inhibitory effects of miR-4775 overexpression on cell viability, migration, and invasion. Overexpression of CDK6 activated the PI3K/AKT/MAPK and Notch signal pathways. Overall, these findings demonstrate that LINC00152 plays an oncogenic role in glioma cells by regulation of miR-4775, which may therefore be a potential therapeutic target for glioma.

Key words: Long intergenic noncoding RNA 152 (LINC00152); MicroRNA 4775 (miR-4775); Glioma; Proliferation; Metastasis; Apoptosis

Address correspondence to Wei Zhou, Department of Neurosurgery, Ningbo No. 2 Hospital, No. 41 Xibei Street, Ningbo, Zhejiang 315010, 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. 869-878, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15123838050075
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Overexpression of Long Noncoding RNA PTENP1 Inhibits Cell Proliferation and Migration via Suppression of miR-19b in Breast Cancer Cells

Xianbiao Shi, Xiaoqiao Tang, and Lei Su

Department of Breast Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, P.R. China

This study aimed to investigate the effect of long noncoding RNA PTENP1 in the development of breast cancer (BC). Quantitative real-time PCR was utilized to determine the expression of PTENP1 in tissues and cell lines. pcDNA3.1 and shRNA were used to over- and low-express PTENP1 in BC cell lines, and miR-19b mimic and inhibitor were utilized to over- and low-express miR-19b. Then the abilities of cell survival, apoptosis, migration, and invasion were assessed in BC cells with different expression levels of PTENP1 and miR-19b. The expression of PTENP1 was significantly downregulated in both BC tissues and cell lines. Overexpressed PTENP1 could significantly increase cell survival, colony forming, migration, and invasion but decrease apoptosis in BC cell lines. However, overexpressed miR-19b performed contrary effects compared with PTENP1 on cell survival, colony forming, migration, invasion, and apoptosis in BC cell lines. miR-19b can be downregulated by PTENP1, and the effect of overexpressed PTENP1 on the PI3k/Akt pathway could be aborted by overexpressed miR-19b. PTENP1 performed a negative role in the development of BC via downregulating miR-19 probably through the PTEN/PI3K/Akt pathway.

Key words: Phosphatase and tensin homolog pseudogene 1 (PTENP1); Breast cancer (BC); MicroRNA-19b (miR-19b); Cell viability; Migration

Address correspondence to Lei Su, Department of Breast Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, 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. 879-888, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15024935181289
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA NEAT1 Promotes Growth and Metastasis of Cholangiocarcinoma Cells

Cheng Zhang,* Jing-Yi Li,* Fu-Zhou Tian,† Gang Zhao,‡ Hai Hu,‡ Yue-Feng Ma,* and Yu-Long Yang*

*Department of Biliary Minimally Invasive Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, P.R. China
†Department of Minimally Invasive Surgery, Tongji University Affiliated Shanghai East Hospital, Shanghai, P.R. China
‡Department of General Surgery, General Hospital of Chengdu Military Command, Chengdu, Sichuan, P.R. China

Long noncoding RNAs (lncRNAs) are known to play important roles in cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis. We investigated the role of nuclear paraspeckleassembly transcript 1 (NEAT1) lncRNA in promoting CCA. qRT-PCR analysis of patient samples showed that NEAT1 expression was higher in CCA tumors than in matched adjacent nontumor tissue. NEAT1 levels were also higher in CCA cell lines than in a normal biliary epithelium cell line (HIBEpic). NEAT1 knockdown in CCA cell lines using shNEAT1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively. CCA cells transfected with shNEAT1 also exhibited reduced metastasis and invasiveness in Transwell assays. NEAT1 knockdown cells produced smaller tumors, demonstrating that NEAT1 promotes tumor growth in vivo. Silencing of NEAT1 increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with NEAT1 expression in CCA tissue samples. RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. We postulate that NEAT1 is a potentially useful diagnostic and therapeutic target for CCA.

Key words: Long noncoding RNAs (lncRNAs); Cholangiocarcinoma (CCA); E-cadherin; Nuclear paraspeckle assembly transcript 1 (NEAT1); Enhancer of zeste homolog 2 (EZH2)

Address correspondence to Yu-Long Yang, Department of Biliary Minimally Invasive Surgery, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Road, Zhongshan District, Dalian, Liaoning Province 116001, 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. 889-899, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15009419625178
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Emodin Induces Apoptosis of Colon Cancer Cells via Induction of Autophagy in a ROS-Dependent Manner

Yuanyuan Wang,*1 Qin Luo,*1 Xianlu He,†1 He Wei,* Ting Wang,* Jichun Shao,‡ and Xinni Jiang*

*Department of Biomedical Sciences, Chengdu Medical College, Chengdu, Sichuan, P.R. China
†Department of General Surgery, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, Sichuan, P.R. China
‡Department of Urology, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, Sichuan, P.R. China

Recent studies revealed that emodin extracted from Chinese herbs exhibits an anticancer effect on different cancer types, including colon cancer. However, the mechanism is not well understood. In our study, we confirmed that emodin treatment inhibited cell viability and induced apoptosis in colon cancer cells. Further experiments found that emodin was also able to induce autophagy, which is indispensible for apoptosis induced by emodin. More interestingly, emodin treatment also results in mitochondrial dysfunction and ROS accumulation in colon cancer cells. Finally, we stressed that ROS accumulation is essential for autophagy and apoptosis induced by emodin. In conclusion, emodin induces apoptosis in colon cancer cells through induction of autophagy, during which ROS generation is of the essence. Our findings improve understanding of emodin’s effect on colon cancer suppression and provide a new theoretical basis for colon cancer therapy.

Key words: Emodin; Colon cancer; Apoptosis; Autophagy; Reactive oxygen species (ROS)

1These authors provided equal contribution to this work.
Address correspondence to Jichun Shao, Department of Urology, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, Sichuan 610051, P.R. China. Tel: (+86) 62739582; Fax: (+86) 62739582; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Xinni Jiang, Department of Biomedical Sciences, Chengdu Medical College, Chengdu, Sichuan 610051, P.R. China. Tel: (+86) 62739582; Fax: (+86) 62739582; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 901-911, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15061902533715
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN

Jianjun Shen,*1 Weina Niu,†1 Hongbo Zhang,* Ma Jun,* and Hongyan Zhang*

*Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, Anhui, P.R. China
†Department of Oncology, Anhui Cancer Hospital, Hefei, Anhui, P.R. China

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the expression patterns, biological roles, and underlying mechanisms of microRNA-147 (miR-147) in gastric cancer. The present study demonstrated that miR-147 was significantly upregulated in gastric cancer tissues and cell lines. Downregulation of miR-147 decreased cell proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-fluorouracil (5-FU) through the cell apoptosis pathway. In addition, phosphatase and tensin homolog (PTEN) was mechanically identified as the direct target of miR-147 in gastric cancer. PTEN knockdown reversed the effects of miR-147 downregulation on the proliferation, chemosensitivity, and 5-FU-induced apoptosis of gastric cancer cells. Moreover, miR-147 regulated the PI3K/AKT signaling pathway in gastric cancer by targeting PTEN. In conclusion, miR-147 suppressed the proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-FU by promoting cell apoptosis through directly targeting PTEN and regulating the PI3K/AKT signaling pathway. This study provides important insight into the molecular mechanism that underlies the chemoresistance of gastric cancer cells. The results of this study could aid the development of a novel therapeutic strategy for gastric cancer.

Key words: Phosphatase and tensin homolog (PTEN); MicroRNA-147 (miR-147); Gastric cancer; Proliferation; Chemosensitivity; 5-Fluorouracil (5-FU)

1These authors provided equal contribution to this work.
Address correspondence to Hongyan Zhang, Department of Radiation Oncology, Anhui Provincial Hospital, No. 17 Lujiang Road, Hefei, Anhui 23001, 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. 913-922, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15135941182107
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MYBL2 Is Targeted by miR-143-3p and Regulates Breast Cancer Cell Proliferation and Apoptosis

Jianli Chen*1 and Xiaowen Chen†1

*The Third Department of Medical Oncology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P.R. China
†Department of Oncology Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, P.R. China

Breast cancer remains a public health issue on a global scale. The present study aimed to explore the functional role of MYB proto-oncogene like 2 (MYBL2) in breast cancer, as well as underlying mechanisms. The regulatory relationship between miR-143-3p and MYBL2 was analyzed, and the effects of dysregulation of miR-143-3p and MYBL2 on cell proliferation and apoptosis were investigated. The results showed that MYBL2 and miR-143-3p were inversely expressed in breast cancer tissues and cells: MYBL2 was highly expressed, whereas miR-143-3p was lowly expressed. MYBL2 was confirmed as a target gene of miR-143-3p. Suppression of MYBL2 inhibited proliferation and induced apoptosis of breast cancer cells, which was similar to the effects of overexpression of miR-143-3p. Our findings reveal that MYBL2 is targeted by miR-143-3p and regulates breast cancer cell proliferation and apoptosis.

Key words: MYB proto-oncogene like 2 (MYBL2); Breast cancer; miR-143-3p; Cell apoptosis; Cell proliferation

1These authors are co-first authors.
Address correspondence to Xiaowen Chen, Department of Oncology Center, Affiliated Hospital of Guangdong Medical College, No. 57 South People’s Avenue, Xiashan District, Zhanjiang, Guangdong 524000, 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. 923-931, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15143731031009
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-206 Inhibits Cell Proliferation, Migration, and Invasion by Targeting BAG3 in Human Cervical Cancer

Yingying Wang*† and Yongjie Tian*

*Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China
†Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China

miR-206 and Bcl-2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. We investigated the expressions and mechanisms of miR-206 and BAG3 in CC using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEECs. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells. Furthermore, miR-206 overexpression repressed cell proliferation, migration, and invasion in vitro, and the 3′-untranslated region (3′-UTR) of BAG3 was a direct target of miR-206. miR-206 overexpression also inhibited EGFR, Bcl-2, and MMP2/9 protein expression, but promoted Bax protein expression. Besides, BAG3 overexpression partially abrogated miR-206-inhibited cell proliferation and invasion, while BAG3 silencing enhanced miR-206-mediated inhibition. In vivo assay revealed that miR-206 repressed tumor growth in nude mice xenograft model. In conclusion, miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human CC. Thus, miR-206-BAG3 can be used as a useful target for CC.

Key words: MicroRNA-206 (miR-206); B-cell lymphoma 2-associated athanogene 3 (BAG3); Cervical cancer

Address correspondence to Yongjie Tian, Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Huaiyin District, Jinan 250021, 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. 933-940, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15144741233346
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-103 Promotes Proliferation and Inhibits Apoptosis in Spinal Osteosarcoma Cells by Targeting p57

Xuesong Wang,* Yong Lin,† Lei Peng,‡ Ruifu Sun,* Xiaojin Gong,* Jinlong Du,* and Xiugong Zhang*

*Department of Spinal, Qingdao Central Hospital, Qingdao, P.R. China
†Department of Spinal, Qingdao Municipal Hospital, Qingdao, P.R. China
‡Library of Qingdao Central Hospital, Qingdao, P.R. China

Osteosarcoma is one of the most aggressive malignancies with poor prognosis rates. Many studies have demonstrated that miRNAs were involved in osteosarcoma, but the role of miR-103a in osteosarcoma remains elusive. In this study, we detected the expression levels of miR-103 in osteosarcoma and non-osteosarcoma tissues and cell lines. The binding effect of miR-103 on p57 was detected by luciferase reporter assay. After altering expressions of miR-103 or p57, viability, migration, invasion, and apoptosis of MG63 cells and expressions of proteins related with the JNK/STAT and mTOR pathways were all detected. We found the higher expression of miR-103 in osteosarcoma tissues and cell lines compared with non-osteosarcoma tissues and cell lines. miR-103 overexpression promoted survival, migration, and invasion of MG63 cells. Knockdown of miR-103a inhibited cell survival, migration, and invasion by upregulating the expression of p57, which was a target of miR-103. Moreover, miR-103a overexpression activated the JNK/STAT and mTOR pathways probably through inhibiting p57 expression. In conclusion, miR-103a acted as an oncogene in osteosarcoma, probably through activating the JNK/STAT and mTORpathways by inhibiting p57 expression.

Key words: Osteosarcoma; miR-103a; p57; Mammalian target of rapamycin (mTOR) pathway; Janus kinase/signal transducer and activator of transcription (JNK/STAT) pathway

Address correspondence to Yong Lin, Department of Spinal, Qingdao Municipal Hospital, No. 1 Jiaozhou Road, Qingdao 266011, 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. 941-948, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X15149775533331
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Ailanthone Promotes Human Vestibular Schwannoma Cell Apoptosis and Autophagy by Downregulation of miR-21

Peizhen Yang,* Dezhong Sun,* and Fei Jiang†

*Department of Otorhinolaryngology, Linyi People’s Hospital, Linyi, Shandong, P.R. China
†Department of Gynecology and Obstetrics, Linyi People’s Hospital, Linyi, Shandong, P.R. China

Ailanthone (AIL) is a quassinoid isolated from the traditional Chinese medicinal herb Ailanthus altissima. The antitumor activities of AIL have been reported in several cancers. The purpose of the present study was to explore the effect of AIL on vestibular schwannomas (VSs). Various concentrations of AIL (0–1 μM) were used to treat human primary VS cells, and then cell viability, proliferation, apoptosis, and autophagy were assessed. Expression of miR-21 in VS cells was altered by miRNA transfection. The functional actions of AIL on miR-21 dysregulated cells were also assessed. AIL significantly reduced the viability of VS cells, and the IC50 value was 0.48 ± 0.023 μM. In response to 0.6 μM AIL, BrdU+ cell rate and cyclin D1 expression were reduced, apoptotic cell rate was increased, caspase 3 and caspase 9 were cleaved, Beclin-1 and LC3-II were accumulated, and p62 was downregulated. miR-21 was lowly expressed in AIL-treated cells, and AIL-induced apoptosis and autophagy were attenuated by miR-21 overexpression. In addition, AIL downregulated Ras and Raf and deactivated MEK, ERK, mTOR, and p70S6K, while the downregulation and deactivation induced by AIL were reversed by miR-21 overexpression. To conclude, AIL inhibited VS cell proliferation and induced apoptosis and autophagy. The antitumor activities of AIL in VS cells were realized possibly via downregulation of miR-21 and blocking the Ras/Raf/MEK/ERK and mTORpathways.

Key words: Vestibular schwannoma (VS); Ailanthone (AIL); miR-21; Apoptosis; Autophagy

Address correspondence to Fei Jiang, Department of Gynecology and Obstetrics, Linyi People’s Hospital, No. 27, East Part of Jiefang Road, Linyi 276003, 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. 949-957, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X15149787144385
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-202 Inhibits Cell Proliferation, Migration, and Invasion by Targeting Epidermal Growth Factor Receptor in Human Bladder Cancer

Liqing Zhang,* Jianjiang Xu,† Gaodi Yang,* Heng Li,‡ and Xiuxia Guo§

*Department of Urology Surgery, General Hospital of Jinan Military Command, Jinan, Shandong, P.R. China
†Department of Pharmacy, General Hospital of Jinan Military Command, Jinan, Shandong, P.R. China
‡Department of Medicine, School of Life Science, Jinan University, Jinan, Shandong, P.R. China
§Department of Gynecology, General Hospital of Jinan Military Command, Jinan, Shandong, P.R. China

Recent studies have demonstrated that miR-202 is associated with several types of cancer; however, the expression and function of miR-202 have not been investigated in bladder cancer. We analyzed the expression of miR-202 in bladder cancer tissues and adjacent noncancerous tissues. The effect of miR-202 on the proliferation, migration, and invasion was evaluated by in vitro assays. The target gene of miR-202 was assessed by luciferase reporter assay. In this study, miR-202 was found to be significantly downregulated in bladder cancer cell lines and tissues and was highly correlated with the T classification, N classification, grade, and recurrence. Ectopic expression of miR-202 suppressed cell viability, colony formation, cell migration, and invasion in vitro and inhibited xenograft tumor growth in vivo. Inversely, downregulation of miR-202 had contradictory effects. The 3¢-untranslated region (3¢-UTR) of epidermal growth factor receptor (EGFR) was identified as a direct target of miR-202 using luciferase reporter assays, and knockdown of EGFR enhanced miR-202-inhibited cell proliferation, migration, and invasion. In conclusion, miR-202 suppresses bladder cancer carcinogenesis and progression by targeting EGFR, thereby representing a potential target for miRNA-based therapy for bladder cancer in the future.

Key words: miR-202; Epidermal growth factor receptor (EGFR); Bladder cancer

Address correspondence to Xiuxia Guo, Department of Gynecology, General Hospital of Jinan Military Command, No. 25 Shifan Road, Jinan 250031, 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. 959-966, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15145624664031
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

T-box Transcription Factor Tbx3 Contributes to Human Hepatocellular Carcinoma Cell Migration and Invasion by Repressing E-Cadherin Expression

Xianguang Feng,* Wenhuan Yao,† Zengzhen Zhang,* Fangshui Yuan,* Li Liang,* Jingqiang Zhou,* Shuang Liu,* and Jiqing Song‡

*Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Tianqiao District, Jinan, Shandong, P.R. China
†Institute of Toxicology and Function Inspection, Shandong Center for Disease Control and Prevention, Lixia District, Jinan, Shandong, P.R. China
‡Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Huaiyin District, Jinan, Shandong, P.R. China

Tbx3, a member of the T-box family of transcription factors, contributes directly to tumor formation, migration, and invasion. However, the role of Tbx3 in the metastasis of HCC remains unclear. In the present study, Tbx3 expression was detected in HCC tissues and cells by Western blot, and Tbx3 expression was regulated by use of siRNAs or lentivirus-mediated vectors. Here we found that Tbx3 protein expression increased in HCC tissues and cell lines. Tbx3 expression was positively associated with multiple tumor nodes, venous infiltration, and advanced TNM tumor stage. Survival analysis demonstrated that Tbx3 expression was an independent prognostic factor for HCC patients. In vitro assays further validated that Tbx3 indeed prompted HCC cell migration and invasion. In addition, Tbx3 expression was negatively related with E-cadherin expression in HCC tissues. Mechanically, Tbx3 inhibited the expression of E-cadherin, and then facilitated epithelial–mesenchymal transition (EMT) of HCC cells. Furthermore, the effect of Tbx3 knockdown on HCC cells was attenuated by E-cadherin knockdown. In conclusion, Tbx3 may be a novel prognostic factor, and it contributes to HCC cell migration, invasion, and EMT by repressing E-cadherin expression. Thus, Tbx3 may be recommended as a therapeutic target for HCC patients.

Key words: Tbx3; E-Cadherin; Metastasis; Hepatocellular carcinoma (HCC)

Address correspondence to Jiqing Song, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Huaiyin District, Jinan 250021, 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. 967-976, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X15148192843443
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-136 Inhibits Malignant Progression of Hepatocellular Carcinoma Cells by Targeting Cyclooxygenase 2

Haiyan Jia,* Hong Wang,† Yanfen Yao,* Chunlei Wang,‡ and Pibao Li*

*Department of Intensive Care Unit, Shandong Provincial Third Hospital, Tianqiao District, Jinan, Shandong, P.R. China
†Department of General Surgery, Shandong Provincial Third Hospital, Tianqiao District, Jinan, Shandong, P.R. China
‡Thyroid Disease Prevention and Control Center, Shandong Provincial Institute of Endemic Disease Control, Lixia District, Jinan, Shandong, P.R. China

MicroRNAs (miRNAs) play a vital role in regulating tumor progression. Dysregulated miR-136 expression was linked to the development of various human cancers. In the present study, we investigated the expression and relationship of miR-136 and COX2 in hepatocellular carcinoma (HCC) using relevant experiments, involving CCK-8, Transwell assay, and luciferase reporter assay. We demonstrated that miR-136 expression is obviously decreased in HCC tissues and cells, and negatively correlated with the expression of COX2 mRNA. In vitro assay revealed that overexpression of miR-136 significantly changed the expression of proliferation- and metastasis-related proteins and inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Dual-luciferase reporter assay validated that the 3′-untranslated region (3′-UTR) of COX2 is a direct target of miR-136. Furthermore, COX2 siRNA partially enhanced the miR-136 overexpression-induced inhibitory effects. In conclusion, miR-136 was vital in the regulation of HCC cell proliferation and metastasis by targeting COX2. Thus, our findings provided novel evidence that miR-136 might be recommended as a potential target for the diagnosis and treatment of HCC patients.

Key words: miR-136; Cyclooxygenase 2 (COX2); Hepatocellular carcinoma (HCC)

Address correspondence to Pibao Li, Department of Intensive Care Unit, Shandong Provincial Third Hospital, No. 12, Central Wuying Hill Road, Tianqiao District, Jinan 250031, 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. 977-985, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X15037506066252
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Overexpression of MicroRNA-34a-5p Inhibits Proliferation and Promotes Apoptosis of Human Cervical Cancer Cells by Downregulation of Bcl-2

Xiufen Wang,*1 Yucui Xie,†1 and Jing Wang‡

*Department of Gynecology, Linzi District People’s Hospital, Zibo, P.R. China
†Department of Reproductive Health and Sterility, Linzi District People’s Hospital, Zibo, P.R. China
‡Department of Gynecology, The Second People Hospital of Dezhou, Dezhou, P.R. China

Aberrant expressions of microRNAs (miRNAs) are involved in the development and progression of various types of cancers. In this study, we investigated the roles of miR-34a-5p in the proliferation, migration, invasion, and apoptosis of cervical cancer cells (HeLa cells). We found that overexpression of miR-34a-5p significantly inhibited the viability, migration, and invasion of HeLa cells, but promoted cell apoptosis. Suppression of miR-34a-5p showed opposite effects. The mRNA and protein expression levels of Bcl-2 in HeLa cells were increased by miR-34a-5p suppression but decreased by miR-34a-5p overexpression. Bcl-2 was a direct target gene of miR-34a-5p, which participated in the effects of miR-34a-5p on HeLa cell viability, migration, invasion, and apoptosis. Suppression of miR-34a-5p promoted the viability, migration, and invasion of HeLa cells by increasing the expression of Bcl-2. Moreover, overexpression of Bcl-2 significantly promoted cell viability, migration, and invasion and had no influence on cell apoptosis. Suppression of Bcl-2 showed the opposite effects, with an increase in apoptosis. Overexpression of Bcl-2 activated the PI3K/AKT and JAK/STAT pathways in cervical cancer cells. Suppression of Bcl-2 inactivated the PI3K/AKT and JAK/STAT pathways in cervical cancer cells.

Key words: MicroRNA-34a-5p; Cell proliferation; Cell apoptosis; Bcl-2; Cervical cancer

1These authors provided equal contribution to this work.

Address correspondence to Jing Wang, Department of Gynecology, The Second People Hospital of Dezhou, No. 55 Fangzhi Street, Canal Economic Development Zone, Dezhou 253000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it