miR‑375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression

Shen,Zhi‑Yong; Zhang,Zi‑Zhen; Liu,Hua; Zhao,En‑Hao; Cao,Hui

doi:10.3892/etm.2014.1627

miR‑375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression

Authors:
- Zhi‑Yong Shen
- Zi‑Zhen Zhang
- Hua Liu
- En‑Hao Zhao
- Hui Cao
View Affiliations

Affiliations: Department of General Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201112, P.R. China
Published online on: March 20, 2014 https://doi.org/10.3892/etm.2014.1627
Pages: 1757-1761

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) are small non‑coding RNA molecules that regulate the expression of targeted genes in a post‑transcriptional manner. Increasing evidence indicates that miRNAs play important roles in cancer pathogenesis, including apoptosis, proliferation and differentiation, as oncogenes or tumor suppressors. Previously, miR‑375 was shown to be involved in human gastric cancer, however, the mechanism remains poorly understood. In the present study, miR‑375 was shown to be downregulated in gastric cancer tissues, particularly human epidermal growth factor receptor 2 (ERBB2)‑positive gastric cancer tissues. Identified by dual luciferase assays and western blot analysis, ERBB2 was demonstrated to be a target gene of miR‑375. In addition, miR‑375 overexpression suppressed the proliferation of human gastric cancer cells in vitro and the suppression effect was restored by ERBB2 overexpression. Thus, the results of the present study indicate that miR‑375 is associated with human gastric carcinogenesis by targeting ERBB2. Therefore, miR‑375 may be used as a potential clinical classification marker and therapeutic target for human gastric cancer.

View Figures

View References

1	Danaei G, Vander Hoorn S, Lopez AD, Murray CJ and Ezzati M; Comparative Risk Assessment collaborating group (Cancers). Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet. 366:1784–1793. 2005. View Article : Google Scholar : PubMed/NCBI
2	Delaunoit T: Latest developments and emerging treatment options in the management of stomach cancer. Cancer Manag Res. 3:257–266. 2011. View Article : Google Scholar : PubMed/NCBI
3	Bang YJ: Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer. J Clin Gastroenterol. 46:637–648. 2012. View Article : Google Scholar : PubMed/NCBI
4	Hofmann M, Stoss O, Shi D, et al: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 52:797–805. 2008. View Article : Google Scholar : PubMed/NCBI
5	Park YS, Hwang HS, Park HJ, et al: Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol. 43:413–422. 2012. View Article : Google Scholar
6	Fassan M, Mastracci L, Grillo F, et al: Early HER2 dysregulation in gastric and oesophageal carcinogenesis. Histopathology. 61:769–776. 2012. View Article : Google Scholar : PubMed/NCBI
7	Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J and Sung JJ: MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene. 29:5761–5771. 2010. View Article : Google Scholar : PubMed/NCBI
8	Nicoloso MS, Spizzo R, Shimizu M, Rossi S and Calin GA: MicroRNAs - the micro steering wheel of tumour metastases. Nat Rev Cancer. 9:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
9	Ueda T, Volinia S, Okumura H, Shimizu M, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar : PubMed/NCBI
10	Avissar M, Christensen BC, Kelsey KT and Marsit CJ: MicroRNA expression ratio is predictive of head and neck squamous cell carcinoma. Clin Cancer Res. 15:2850–2855. 2009. View Article : Google Scholar : PubMed/NCBI
11	Mathé EA, Nguyen GH, Bowman ED, Zhao Y, et al: MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 15:6192–6200. 2009.PubMed/NCBI
12	Liu AM, Poon RT and Luk JM: MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties. Biochem Biophys Res Commun. 394:623–627. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ding L, Xu Y, Zhang W, Deng Y, et al: MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res. 20:784–793. 2010. View Article : Google Scholar : PubMed/NCBI
14	Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, et al: MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 70:2339–2349. 2010. View Article : Google Scholar : PubMed/NCBI
15	Washington K: 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 17:3077–3079. 2010. View Article : Google Scholar : PubMed/NCBI
16	Rüschoff J, Hanna W, Bilous M, Hofmann M, et al: HER2 testing in gastric cancer: a practical approach. Mod Pathol. 25:637–650. 2012.PubMed/NCBI