TITLE

Sensitization of Gastric Cancer Cells to 5-FU by MicroRNA-204 Through Targeting the TGFBR2-Mediated Epithelial to Mesenchymal Transition

AUTHOR(S)
Li, Liang-Qing; Pan, Dun; Chen, Qun; Zhang, Sheng-Wei; Xie, Di-Ya; Zheng, Xue-Lan; Chen, Hui
PUB. DATE
July 2018
SOURCE
Cellular Physiology & Biochemistry (Karger AG);Jul2018, Vol. 47 Issue 4, p1533
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background/Aims: Gastric cancer (GC) is the most common gastrointestinal malignancy, causing cancer-related deaths in East Asia. MicroRNAs (miRNAs) are small non-coding RNAs aberrantly expressed in human tumors. In this study, we aim to investigate the roles of miR-204 in the epithelial to mesenchymal transition (EMT)-associated chemosensitivity. Methods: The expression of miR-204 was detected in clinical tumor samples and GC cell lines by real time PCR. Tumor cell’s growth, invasion, and migration were measured by MTT assay, wound healing assay, and transwell invasion assay, respectively. Western blot method was used to detect the protein levels of indicated genes. Luciferase reporter assay was performed to validate the target gene of miR-204. The in vivo role of miR-204 was measured using a xenograft mouse model of GC. Results: By comparing the expressions of miR-204 in human gastric tumors and their adjacent normal tissues, it was disclosed that miR-204 was significantly downregulated in gastric tumors. Moreover, miR-204 was downregulated in multiple GC cell lines compared with normal gastric epithelial cells. Overexpression of miR-204 suppressed GC cells’ proliferation, invasion, and migration. It is noteworthy that 5-FU treatments induced miR-204 expression and suppressed TGF-β pathway. By establishment of 5-FU resistant GC cell line, it was revealed that miR-204 was significantly downregulated in 5-FU resistant GC cells, representing mesenchymal features with downregulation of epithelial marker, while mesenchymal markers were upregulated. We identified TGFBR2 as a direct target of miR-204 by Western blot method and luciferase assay in GC cells and tumor samples as well. In addition, overexpression of miR-204 sensitized GC cells to 5-FU in vitro. Xenograft experiments demonstrated that the combination of miR-204 and 5-FU efficiently inhibited tumor growth and improved survival rate of mice as well. Eventually, we illustrated the restoration of TGFBR2 in miR-204 overexpression GC cells, which recovered resistance to 5-FU treatments compared with miR-204 overexpression GC cells. Conclusion: This study describes a miRNA-based therapeutic strategy against 5-FU resistance in GC, contributing to the development of anti-chemoresistance therapeutic agents.
ACCESSION #
130931610

 

Related Articles

  • microRNA-32 inhibits the proliferation and invasion of the SGC-7901 gastric cancer cell line in vitro. JIANFENG ZHANG; XIAOLING KUAI; MENGJIAO SONG; XIAOQI CHEN; ZHIHUA YU; HONG ZHANG; ZHENBIAO MAO // Oncology Letters;2014, Vol. 7 Issue 1, p270 

    microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs, which suppress their target mRNAs at the post-transcriptional level. miRNAs play key roles in tumor metastasis. The aim of the present study was to investigate the expression of miRNA-32 (miR-32) on the biological...

  • 微小 RNA-30e 调控EMT对胃癌侵袭和迁移影响的研究. 章萧; 艾芬; 张莉红; 刘迪; 张佩雯 // Progress in Modern Biomedicine;Nov2019, Vol. 19 Issue 22, p4208 

    Objective: To investigate the effect of microRNA-30e (miR-30e) on the invasion and migration of gastric cancer and the potential mechanism. Mrthods: The transwell system and the assays of wound healing were used to assess the invasion and migration ability of gastric cell line BGC823. The...

  • MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis. Wu, Jian-Guo; Wang, Jin-Jie; Jiang, Xin; Lan, Jian-Ping; He, Xu-Jun; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Ru, Guo-Qing; Ma, Jie; Zhao, Zhong-Sheng; Zhou, Ren // Gastric Cancer;Oct2015, Vol. 18 Issue 4, p729 

    Background: MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathway s of MiR-125b in gastric cancer. Methods: We...

  • DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Li, Zheng; Lei, Huizi; Luo, Min; Wang, Yi; Dong, Lei; Ma, Yanni; Liu, Changzheng; Song, Wei; Wang, Fang; Zhang, Junwu; Shen, Jianxiong; Yu, Jia // Gastric Cancer;Jan2015, Vol. 18 Issue 1, p43 

    Background: MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as...

  • miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF. Chen, Bitao; Huang, Tao; Jiang, Jun; Lv, Lei; Li, Hongxing; Xia, Shitao // Molecular & Cellular Biochemistry;Mar2014, Vol. 388 Issue 1/2, p211 

    miR-141 belongs to the miR-200 family, and has been found to be associated with numerous human malignancies; however, its role in gastric cancer (GC) has not been examined in detail. Here, we validated that miR-141 was decreased in GC tissues and cell lines. Forced expression of miR-141...

  • MicroRNA-495 suppresses human renal cell carcinoma malignancy by targeting SATB1. Cai Lv; Zhiming Bai; Zhenxiang Liu; Pengcheng Luo; Jie Zhang // American Journal of Translational Research;2015, Vol. 7 Issue 10, p1992 

    Deregulated expression of miRNAs is related to progression and initiation of human cancers. Although miR-495 has identified in various tumors, its expression and function in renal cell carcinoma (RCC) is still unknown. In this study, we found that the expression of miR-495 was downregulated in...

  • Impact of BTG2 expression on proliferation and invasion of gastric cancer cells in vitro. Zhang, Lin; Huang, Haili; Wu, Kai; Wang, Mengwei; Wu, Benyan // Molecular Biology Reports;Jul2010, Vol. 37 Issue 6, p2579 

    BTG2 (B cell translocation gene 2) is downregulated in several human tumors and has been known as a tumor suppressor in carcinogenesis of thymus, prostate, kidney, and liver. However, little is known about the role BTG2 plays in gastric adenocarcinoma. In the present study, we intended to...

  • microRNA-503 inhibits gastric cancer cell growth and epithelial-to-mesenchymal transition. YANG PENG; YAN-MIN LIU; LU-CHUN LI; LU-LU WANG; XIAO-LING WU // Oncology Letters;2014, Vol. 7 Issue 4, p1233 

    Epithelial-to-mesenchymal transition (EMT) is believed to be associated with cancer cell malignancy, and also to cause cancer invasion and metastasis. Recent evidence indicates that small non-protein coding RNA [microRNAs (miRNAs/miRs)] may act as powerful regulators of EMT. The present study...

  • The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer. Zhou, Xiaoying; Ye, Feng; Yin, Chengqiang; Zhuang, Ya; Yue, Ge; Zhang, Guoxin // Cellular Physiology & Biochemistry (Karger AG);Jul2015, Vol. 36 Issue 4, p1440 

    Background/Aims: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics