Oncology Research 27(2) Abstracts

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Oncology Research, Vol. 27, pp. 139-146, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15185747911701
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Liquiritigenin Inhibits Colorectal Cancer Proliferation, Invasion, and Epithelial-to-Mesenchymal Transition by Decreasing Expression of Runt-Related Transcription Factor 2

Fan-Chun Meng and Jun-Kai Lin

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

Inhibition of tumor metastasis is one of the most important purposes in colorectal cancer (CRC) treatment. This study aimed to explore the effects of liquiritigenin, a flavonoid extracted from the roots of
Glycyrrhiza uralensis Fisch, on HCT116 cell proliferation, invasion, and epithelial-to-mesenchymal transition (EMT). We found that liquiritigenin significantly inhibited HCT116 cell proliferation, invasion, and the EMT process, but had no influence on cell apoptosis. Moreover, liquiritigeninremarkably reduced the expression of runt-related transcription factor 2 (Runx2) in HCT116 cells. Overexpression of Runx2 obviously reversed the liquiritigen-ininduced invasion and EMT inhibition. Furthermore, liquiritigenin inactivated the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in HCT116 cells. Upregulation of Runx2 reversed the liquiritigen-ininduced PI3K/AKT pathway inactivation. In conclusion, our research verified that liquiritigenin exerted significant inhibitory effects on CRC invasion and EMT process by downregulating the expression of Runx2 and inactivating the PI3K/AKT signaling pathway. Liquiritigenin could be an effective therapeutic and preventative medicine for CRC treatment.

Key words: Colorectal cancer (CRC); Liquiritigenin; Epithelial-to-mesenchymal transition (EMT); Runt-related transcription factor 2; PI3K/AKT signaling pathway

Address correspondence to Jun-Kai Lin, Department of Gastrointestinal Surgery, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying District, 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. 27, pp. 147-155, 2019
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DOI: https://doi.org/10.3727/096504017X
15021536183517
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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miR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression

Zheng-Gang Chen,* Chuan-Yi Zheng,* Wang-Qing Cai,† Da-Wei Li,* Fu-Yue Ye,* Jian Zhou,* Ran Wu,* and Kun Yang*

*Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, P.R. China
†Department of Neurosurgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China

Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA-26b (miR-26b)/cyclooxygenase-2 (COX-2) axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of the miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased levels of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting a miR-26b mimic into U-373 cells. The invasive cell number and wound closing rate were reduced in U-373 cells transfected with miR-26b mimic. In addition, COX-2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume, and expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for the treatment of glioma.

Key words: MicroRNA 26b (miR-26b); Glioma; Cyclooxygenase 2 (COX-2); Invasion; Migration; Extracellular signal-regulated kinase (ERK)

Address correspondence to Kun Yang, Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical College, No. 23 Longhua Road, Longhua District, Haikou, Hainan 570102, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 157-163, 2019
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DOI: https://doi.org/10.3727/096504018X
15190861873459
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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miR-363-3p Inhibits Osteosarcoma Cell Proliferation and Invasion via Targeting SOX4

Kejun Wang,*1 Lin Yan,*1 and Fen Lu†

*Department of Orthopedics, Jingzhou Central Hospital, Jingzhou, Hubei Province, P.R. China
†The First People’s Hospital of JingzhouJingzhou, Hubei Province, P.R. China

miR-363-3p has been shown to suppress tumor growth and metastasis in various human cancers. However, the function of miR-363-3p in osteosarcoma (OS) has not been determined. In our study, we found that the expression of miR-363-3p was significantly downregulated in OS tissues compared with adjacent normal tissues. miR-363-3p expression was associated with the poor overall survival rate of OS patients. Moreover, we found that overexpression of miR-363-3p markedly inhibited the proliferation, migration, and invasion of U2OS and MG63 cells. Moreover, we found that SOX4 was a direct target of miR-363-3p in OS cells. Overexpression of miR-363-3p significantly inhibited the expression of SOX4. Expression levels of miR-363-3p and SOX4 were negatively correlated in OS tissues. Finally, we found that restoration of SOX4 attenuated the suppressive effects of miR-363-3p on the proliferation, migration, and invasion of U2OS and MG63 cells. Therefore, our findings demonstrated that miR-363-3p served as a tumor suppressor in OS tissues by targeting SOX4.

Key words: miR-363-3p; Proliferation; Invasion; SOX4; Osteosarcoma (OS)

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Fen Lu, The First People’s Hospital of Jingzhou, No. 8 Air Road, Shashi District, Jingzhou 434020, Hubei Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 165-171, 2019
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DOI: https://doi.org/10.3727/096504018X
15193506006164
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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miR-30c Impedes Glioblastoma Cell Proliferation and Migration by Targeting SOX9

Shihui Liu, Xiuxiu Li, and Sujing Zhuang

Department of Neurology, Linyi Central Hospital, Linyi, Shandong Province, P.R. China

miR-30c has been acknowledged as a tumor suppressor in various human cancers, such as ovarian cancer, gastric cancer, and prostate cancer. However, the role of miR-30c in glioblastoma (GBM) needs to be investigated. In our study, we found that the expression of miR-30c was significantly downregulated in GBM tissues and cell lines. We found that overexpression of miR-30c inhibited cellular proliferation of GBM cells in vitro and in vivo. More GBM cells were arrested in the G
0 phase after miR-30c overexpression. Moreover, we showed that miR-30c overexpression suppressed the migration and invasion of GBM cells. Mechanistically, we found that SOX9 was a direct target of miR-30c in GBM cells. Overexpression of miR-30c inhibited the mRNA and protein levels of SOX9 in GBM cells. Moreover, there was a negative correlation between the expression of miR-30c and SOX9 in GBM tissues. Finally, we showed that restoration of SOX9 in GBM cells reversed the proliferation, migration, and invasion of GBM cells transfected with miR-30c mimic. Collectively, our results demonstrated that miR-30c suppressed the proliferation, migration, and invasion of GBM cells via targeting SOX9.

Key words: miR-30c; Proliferation; Migration; SOX9; Glioblastoma

Address correspondence to Sujing Zhuang, Department of Neurology, Linyi Central Hospital, No. 17 Jiankang Road, Yishui County, Linyi 276400, Shandong Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 173-182, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15202945197589
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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H19 Facilitates Tongue Squamous Cell Carcinoma Migration and Invasion via Sponging miR-let-7

Ni Kou,*1 Sha Liu,*1 Xiaojie Li,* Wuwei Li,* Weijian Zhong,* Lin Gui,* Songling Chai,* Xiang Ren,* Risu Na,* Tao Zeng,† and Huiying Liu*

*College of Stomatology, Dalian Medical University, Dalian, Liaoning, P.R. China
†Department of Stomatology, Dalian Stomatological Hospital, Dalian, Liaoning, P.R. China

The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.

Key words: H19; HMGA2; Epithelial–mesenchymal transition (EMT); Migration; Invasion; Tongue squamous cell carcinoma (TSCC)

1These authors provided equal contribution to this work.
Address correspondence to Huiying Liu, College of Stomatology, Dalian Medical University, No. 9 Lvshun Southern Road, Lvshun District, Dalian, Liaoning 116044, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 183-192, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15201124340860
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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MicroRNA-377 Targets Zinc Finger E-box-Binding Homeobox 2 to Inhibit Cell Proliferation and Invasion of Cervical Cancer

Cong Ye,* Yubo Hu,† and Junrong Wang*

*Department of Obstetrics and Gynecology, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China
†Department of Anesthesiology, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China

A large number of microRNAs (miRNAs) are aberrantly expressed in cervical cancer and play crucial roles in the onset and progression of cervical cancer by acting as either an oncogene or a tumor suppressor. Therefore, investigation of the expression, biological roles, and underlying mechanisms of miRNAs in cervical cancer might provide valuable therapeutic targets in the treatment for patients with this disease. In this study, miRNA-377 (miR-377) was downregulated in cervical cancer tissues and cell lines. Decreased miR-377 expression was strongly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis in patients with cervical cancer. Enhanced expression of miR-377 prohibited cell proliferation and invasion in cervical cancer. Bioinformatics analysis predicted that zinc finger E-box-binding homeobox 2 (ZEB2) was a potential target of miR-377. Subsequent experiments confirmed that ZEB2 is a direct target gene of miR-377 in cervical cancer. In addition, ZEB2 was overexpressed in cervical cancer tissues and was inversely related with miR-377 levels. Furthermore, the suppressive effects of miR-377 on cervical cancer proliferation and invasion were rescued by restored ZEB2 expression. Overall, our findings indicated that miR-377 decreases proliferation and invasion of cervical cancer cells by directly targeting ZEB2 and provides novel evidence of miR-377 as a novel therapeutic strategy for the therapy of patients with this malignancy.

Key words: Cervical cancer; MicroRNA-377; Zinc finger E-box-binding homeobox 2 (ZEB2); Proliferation; Invasion

Address correspondence to Junrong Wang, Department of Obstetrics and Gynecology, China–Japan Union Hospital of 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. 27, pp. 193-202, 2019
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DOI: https://doi.org/10.3727/096504018X
15150662230295
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Emodin Inhibits Colon Cancer Cell Invasion and Migration by Suppressing Epithelial–Mesenchymal Transition via the Wnt/β-Catenin Pathway

Juan Gu,* Chang-fu Cui,† Li Yang,‡ Ling Wang,* and Xue-hua Jiang*

*Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, Sichuan, P.R. China
†Department of Neurology, Research Institute of China Weapons Industry, 521 Hospital, Shanxi, P.R. China
‡Microbiological Laboratory, Xinyang Vocational and Technical College, Henan, P.R. China

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo
. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and β-catenin. Emodin also significantly inhibited the activation of the Wnt/β-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/β-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/β-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/β-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/β-catenin signaling pathway.

Key words: Emodin; Colon cancer (CC); Invasion; Migration; Epithelial–mesenchymal transition (EMT); Wnt/β-catenin

Address correspondence to Xue-hua Jiang, Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, No. 3, Section 17, Renmin South Road, Wuhou District, Chengdu, Sichuan 646000, P.R. China. Tel: 028-85501370; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 203-210, 2019
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DOI: https://doi.org/10.3727/096504018X
15202953107093
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Adjuvant Chemotherapy Following Surgical Resection Improves Survival in Patients With Early Stage Small Cell Lung Cancer

Yuanshan Yao, Yinjie Zhou, Zhenhua Yang, Hongbo Huang, and Haibo Shen

Department of Thoracic Surgery, Ningbo No. 2 Hospital, Zhejiang Province, P.R. China

The purpose of this study was to determine the effects of resection coupled with standard chemotherapy on the survival prognosis of patients with early stage small cell lung carcinoma (SCLC). Patients (
n = 110) with mediastinal lymph node-negative SCLC were enrolled in this study. The baseline clinical data of patients with surgery were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were measured by Kaplan–Meier and log-rank test analyses. Ninety-eight patients received mediastinoscopy biopsy, and pulmonary lobectomy or sublobar resection, and 67 patients underwent adjuvant chemotherapy after pulmonary lobectomy. Adjuvant chemotherapy after surgical intervention was associated with longer OS (median OS: 42.14 vs. 33.53 months, p = 0.01) and PFS (median PFS: 25.20 vs. 13.48 months, p = 0.000) compared to resection alone for all patients. Adjuvant chemotherapy was associated with improvement of survival for N1 patients with stage II (median OS: 36.42 vs. 26.68 months, p = 0.021). The median PFS was 19.02 m (16.08, 21.96) and 13.25 m (10.19, 16.30) (p = 0.031), respectively, for patients of N1 stage who received chemotherapy and those who did not. Cox regression analysis demonstrated that age, TNM stage (N stage, not T stage), and chemotherapy were independent risk factors that might affect overall survival in patients with mediastinal lymph node-negative SCLC. These findings suggest that the application of adjuvant chemotherapy following pulmonary lobectomy is associated with improvements of survival prognoses for patients with SCLC. The combination of surgical intervention with conventional therapy should be taken into consideration as a prospective multidisciplinary regimen for early stage SCLC.

Key words: Small cell lung carcinoma (SCLC); Chemotherapy; Lymph node; Survival prognosis; Surgical resection

Address correspondence to Haibo Shen, Department of Thoracic Surgery, Ningbo No. 2 Hospital, No. 41 Northwest Street, Ningbo, Zhejiang Province 315010, P.R. China. Tel: 86-0574-83871083; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 211-218, 2019
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DOI: https://doi.org/10.3727/096504018X
15208993118389
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Thrombospondin 1 Triggers Osteosarcoma Cell Metastasis and Tumor Angiogenesis

Yue Kui Jian,1 Huan Ye Zhu,1 Xing Lin Wu, and Bo Li

Affiliated People’s Hospital of Guizhou Medical University, Guiyang, P.R. China

Osteosarcomas, especially those with metastatic or unresectable disease, have limited treatment options. The antitumor effects of pharmacologic inhibitors of angiogenesis in osteosarcomas are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here we demonstrated that thrombospondin 1 (TSP-1) is a potent inhibitor of the growth and metastasis of the osteosarcoma cell line MG-63. Moreover, we demonstrate that upregulation of TSP-1 facilitated expression of vasculostatin in MG-63 cells. In angiogenesis assays, overexpression of TSP-1 inhibited MG-63 cells and induced tube formation of human umbilical vein endothelial cells (HUVECs) in a CD36-dependent fashion. Finally, in xenografted tumors, we observed that TSP-1 overexpression inhibited angiogenesis and tumor growth. These results provided strong evidence for an important role of the TSP-1/CD36/vasculostatin signaling axis in mediating the antiangiogenic activity of osteosarcoma.

Key words: TSP-1; Osteosarcoma; Metastasis; Angiogenesis; CD36

1These authors provided equal contribution to this work.
Address correspondence to Bo Li, Affiliated People’s Hospital of Guizhou Medical University, No. 83 Zhongshan East Road, Guiyang 550002, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 219-226, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15213126075068
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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Long Noncoding RNA FOXC2-AS1 Predicts Poor Survival in Breast Cancer Patients and Promotes Cell Proliferation

Haisong Yang,* Tengxiang Chen,† Shu Xu,‡ Shiyong Zhang,* and Mengmeng Zhang*

*Department of Breast Surgery, the Affiliated Hospital of Guizhou Medical University, Guizhou, P.R. China
†Department of Physiology, Guizhou Medical University, Guizhou, P.R. China
‡Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guizhou, P.R. China

Breast cancer (BC) is the most common malignant tumor in women. Recently, long noncoding RNAs (lncRNAs) have been proposed as critical regulators in biological processes, including tumorigenesis. FOXC2-AS1, a single antisense oligonucleotide RNA transcribed from the negative strand of forkhead box protein C2 (FOXC2), has been identified as an oncogene in osteosarcoma. In the present study, we investigated the prognosis value and biological role of FOXC2-AS1 in BC. Our findings revealed that FOXC2-AS1 was significantly increased in BC tissues and cell lines, and Kaplan–Meier survival analysis indicated that a high level of FOXC2-AS1 was associated with poor prognosis of BC patients. Loss of function revealed that silenced FOXC2-AS1 significantly suppressed the proliferation ability, and flow cytometric analysis illustrated the influence of FOXC2-AS1 on cell cycle and apoptosis rate. Finally, we found that cyclin D1, cyclin D2, and cyclin D3 were all partly positively modulated by FOXC2-AS1 in BC. Collectively, FOXC2-AS1 may serve as a promising prognostic biomarker and therapeutic target for BC patients.

Key words: Breast cancer (BC); FOXC2-AS1; Prognosis; Proliferation

Address correspondence to Haisong Yang, Department of Breast Surgery, the Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, Guizhou 550004, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 227-235, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15213089759999
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
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miR-449a Suppresses Tumor Growth, Migration, and Invasion in Non-Small Cell Lung Cancer by Targeting a HMGB1-Mediated NF-κB Signaling Pathway

Dandan Wu,*1 Jun Liu,†1 Jianliang Chen,* Haiyan He,* Hang Ma,* and Xuedong Lv*

*Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China
†Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China

MicroRNAs (miRNAs) have been reported to be involved in many human cancers and tumor progression. The dysregulation of miR-449a is found in many types of malignancies and is associated with tumor growth, migration, and invasion. However, its expression and function in non-small cell lung cancer (NSCLC) still remains unclear. In our study, miR-449a was found to be downregulated in both NSCLC tissues and cell lines, and low miR-449a expression was obviously associated with tumor differentiation, TMN stage, and poor overall survival (OS). Moreover, we demonstrated that miR-449a could inhibit tumor proliferation, migration, and invasion in NSCLC. We also confirmed that HMGB1 was a direct target gene of miR-449a in NSCLC with dual-luciferase reporter assay, and upregulation of HMGB1 could reverse the miR-449a-induced suppression of growth, migration, and invasion in NSCLC cells. Last, we found that miR-449a suppressed tumor initiation and development through the NF-
κB signaling pathway. These results indicate that miR-449a functions as a tumor suppressor in NSCLC by targeting the HMGB1-mediated NF-κB signaling pathway in NSCLC.

Key words: miR-449a; Non-small cell lung cancer (NSCLC); High-mobility group box 1 (HMGB1); NF-κB

1These authors provided equal contribution to this work.
Address correspondence to Xuedong Lv, Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, No. 6 Haierxiang North Road, Nantong 226001, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 237-251, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15235274183790
E-ISSN 1555-3906
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Experimental and In Silico Analysis of Cordycepin and its Derivatives as Endometrial Cancer Treatment

Pedro Fong,*1 Cheng N. Ao,*†1 Kai I. Tou,* Ka M. Huang,* Chi C. Cheong,* and Li R. Meng*

*School of Health Sciences, Macao Polytechnic Institute, Macao, P.R. China
†State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, P.R. China

The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancer cell growth. Cytotoxicity MTT assays, clonogenic assays, and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin, and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer.

Key words: Adenosine deaminase; Cordycepin; Docking; Endometrial cancer; Herbal medicines

1These authors provided equal contribution to this work.
Address correspondence to Li R. Meng, School of Health Sciences, Macao Polytechnic Institute, Meng Tak Building, Room 730, Rua de Luis Gonzaga Gomes, Macao, P.R. China. Tel: +853-85993449; Fax: +853-28753159; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 253-260, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15242763477504
E-ISSN 1555-3906
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miR-1284 Inhibits the Growth and Invasion of Breast Cancer Cells by Targeting ZIC2

Pengcheng Zhang,* Fang Yang,† Qin Luo,‡ Daxue Yan,§ and Shengrong Sun*

*Department of Breast Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, P.R. China
†Department of Nursing, Xiangyang No. 1 People’s Hospital of Hubei University of Medicine, Xiangyang, Hubei Province, P.R. China
‡Department of Neonatal Intensive Care Unit, Xiangyang No. 1 People’s Hospital of Hubei University of Medicine, Xiangyang, Hubei Province, P.R. China
§Department of Breast Thyroid Surgery, Xiangyang No. 1 People’s Hospital of Hubei University of Medicine, Xiangyang, Hubei Province, P.R. China

miR-1284 has been reported to inhibit tumor growth in some human cancers, including lung cancer, ovarian cancer, and gastric cancer. Whether it regulates breast cancer progression remains elusive. In this study, we found that miR-1284 was downregulated in breast cancer tissues and cell lines compared to normal control cells. Moreover, we showed that overexpression of miR-1284 significantly inhibited the proliferation, migration, and invasion of breast cancer cells while promoting apoptosis. In terms of mechanism, we found that transcription factor ZIC2 was a target of miR-1284 in breast cancer cells. Through the luciferase reporter assay, we demonstrated their direct interaction. RT-qPCR and Western blot also indicated that miR-1284 overexpression inhibited the protein levels of ZIC2 in breast cancer cells. Moreover, we found that ZIC2 knockdown inhibited the proliferation, migration, and invasion of breast cancer cells, whereas restoration of ZIC2 reversed the effects of miR-1284 on breast cancer cells. Taken together, our findings demonstrated that miR-1284 suppressed the proliferation, migration, and invasion of breast cancer cells via targeting ZIC2, which provided a new insight on the development of therapeutic targets for breast cancer treatment.

Key words: Breast cancer; miR-1284; Proliferation; Migration; ZIC2

Address correspondence to Shengrong Sun, Department of Breast Thyroid Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan 430060, Hubei Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 261-268, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15219188894056
E-ISSN 1555-3906
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miR-223-5p Suppresses Tumor Growth and Metastasis in Non-Small Cell Lung Cancer by Targeting E2F8

Liyan Dou,*1 Kaiyu Han,†1 Mochao Xiao,* and Fuzhen Lv

*Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
†Department of Respiratory Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China

miR-223-5p has been demonstrated to regulate the development and progression of various cancers, such as hepatocellular carcinoma, breast cancer, and gastric carcinoma. However, the role of miR-223-5p in non-small cell lung cancer (NSCLC) requires further investigation. In this study, we found that the expression of miR-223-5p was significantly downregulated in NSCLC tissues and cell lines. Moreover, the expression level of miR-223-5p is negatively correlated with the malignance of NSCLC. We found that overexpression of miR-223-5p remarkably suppressed the proliferation of NSCLC cells in vitro and in vivo. miR-223-5p overexpression also led to reduced migration and invasion in NSCLC cells. Mechanistically, we found that E2F8, a key transcription factor involved in many kinds of biological processes, was a direct target gene of miR-223-5p. Overexpression of miR-223-5p significantly decreased the mRNA and protein levels of E2F8 in NSCLC cells. We also showed that restoration of E2F8 rescued the proliferation, migration, and invasion of miR-223-5p-overexpressing NSCLC cells. Taken together, our findings demonstrated that miR-223-5p suppressed NSCLC progression through targeting E2F8.

Key words: miR-223-5p; Non-small cell lung cancer (NSCLC); Growth; Metastasis; E2F8

1These authors provided equal contribution to this work.
Address correspondence to Fuzhen Lv, Department of Respiratory Medicine, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, P.R. China. Tel: 0451-86605805. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 261-279, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15215019227688
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA 615-3p Inhibits the Tumor Growth and Metastasis of NSCLC via Inhibiting IGF2

Jiangtao Liu,* Yanli Jia,* Lijuan Jia,* Tingting Li,† Lei Yang,‡ and Gongwen Zhang‡

*Medical Oncology, Binzhou Central Hospital, Binzhou, Shandong, P.R. China
†Department of Anesthesiology, Binzhou Central Hospital, Binzhou, Shandong, P.R. China
‡Department of Cardiothoracic Surgery, Binzhou Central Hospital, Binzhou, Shandong, P.R. China

MicroRNAs are essential regulators of cancer-associated genes at the posttranscriptional level, and their expression is altered in cancer tissues. Herein we sought to identify the regulation of miR-615-3p in NSCLC progression and its mechanism. miR-615-3p expression was significantly downregulated in NSCLC tissue compared to control normal tissue. Exogenous overexpression of miR-615-3p inhibited the growth and metastasis of NSCLC cells. In addition, the in vivo mouse xenograft model showed that overexpression of miR-615-3p inhibited NSCLC growth and lung metastasis, whereas decreased expression of miR-615-3p caused an opposite outcome. Furthermore, we revealed that insulin-like growth factor 2 (IGF2) expression was negatively correlated with the miR-615-3p level in NSCLC specimens, and IGF2 knockdown mimicked the effect of miR-615-3p inhibition on NSCLC cell proliferation, migration, and invasion. In addition, overexpression of IGF2 rescued the inhibition of miR-615-3p in NSCLC cells. Together, our results indicated that miR-615-3p played important roles in the regulation of NSCLC growth and metastasis by targeting IGF2.

Key words: Non-small cell lung cancer (NSCLC); miR-615-3p; IGF2; Metastasis

Address correspondence to Gongwen Zhang, Department of Cardiothoracic Surgery, Binzhou Central Hospital, 108 Huangchengnan Road, HuiminBinzhou, Shandong 251700, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 27, pp. 281-282, 2019
0965-0407/19 $90.00 +.00
DOI: https://doi.org/10.3727/096504019X
15476499940873
E-ISSN 1555-3906
Copyright ©2019 Cognizant, LLC.
Printed in the USA. All rights reserved.

Erratum

The following was originally published in Volume 25, Number 1, pages 1–10 (DOI: https://doi.org/10.3727/0965040 16X14685034103798). Information in Figure 5C was incorrectly displayed. The corrected Figure 5 is provided here.

MicroRNA-200a Suppresses Cell Invasion and Migration by Directly Targeting GAB1 in Hepatocellular Carcinoma

Jianlin Wang,*1 Wenjie Song,*1 Weiwei Shen,†1 Xisheng Yang,* Wei Sun,* Sshibin Qu,* Runze Shang,* Ben Ma,* Meng Pu,* Kaishan Tao,* Kefeng Dou,* and Haimin Li*

*Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China
†Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

MicroRNA-200a (miR-200a) is frequently downregulated in most cancer types and plays an important role in carcinogenesis and cancer progression. In this study, we determined that miR-200a was downregulated in hepatocellular carcinoma (HCC) tissues and cell lines, consistent with the results of our previous study. Because a previous study suggested that downregulation of miR-200a is correlated with HCC metastasis, we aimed to elucidate the mechanism underlying the role of miR-200a in metastasis in HCC. Here we observed that overexpression of miR-200a resulted in suppression of HCC metastatic ability, including HCC cell migration, invasion, and metastasis, in vitro and in vivo. Furthermore, bioinformatics and luciferase reporter assays indicated that GAB1 is a direct target of miR-200a. Inhibition of GAB1 resulted in substantially decreased cell invasion and migration similar to that observed with overexpression of miR-200a in HCC cell lines, whereas restoration of GAB1 partially rescued the inhibitory effects of miR-200a. Taken together, these data provide novel information for comprehending the tumor-suppressive role of miR-200a in HCC pathogenesis through inhibition of GAB1 translation.

Key words: miR-200a; Hepatocellular carcinoma (HCC); Grb2-associated binding protein 1 (GAB1); Invasion and migration; Metastasis

1These authors provided equal contribution to this work.
Address correspondence to Haimin Li, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Changle Street, Xi’an, Shaanxi 710032, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Kefeng Dou, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Changle Street, Xi’an, Shaanxi 710032, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it