Original Article

Regulation of miR-596 on the Apoptosis of Gastric Cancer Cells through Its Targeting Inhibition of BCL-2

Abstract

Background: We aimed to investigate the relationship between miR-596, BCL-2, and apoptosis of gastric cancer cells, and to explore the mechanism of miR-596 in gastric cancer. Besides, this study aimed to find the target of miR-596 and explore the mechanism of action of miR-596 in gastric cancer.

Methods: Eighteen samples of gastric cancer tissues and 18 samples of corresponding tumor-adjacent tissues were collected from 18 gastric cancer patients (aged from 40 to 55 yr) admitted to Zhuji People's Hospital, Zhuji, China from March 2017 to May 2018. The expression levels of miR-596 and BCL-2 were detected to verify the regulation of miR-596 on the apoptosis and proliferation of gastric cancer cell lines MKN-45 and HGC-27 and its effect on BCL-2 expression. 

Results: The expression level of miR-596 was notably lower in gastric cancer tissues than in adjacent tissues, and BCL-2 level was notably higher in gastric cancer tissues than in adjacent tissues. After the up-regulation of miR-596 expression, the proliferation of MKN-45 and HGC-27 cells was significantly decreased, the level of apoptosis was significantly increased (P<0.05), and the expression of BCL-2 was decreased. The dual-luciferase report showed that miR-596 had a targeting inhibition of BCL-2. Gastric cancer cells with up-regulated miR-596 and BCL-2 had significantly higher proliferation and lower apoptosis than cells with up-regulated miR-596.

Conclusions: miR-596 can inhibit the proliferation of gastric cancer cells and promote the apoptosis through its targeting inhibition of BCL-2 expression.

1. Smyth EC, Verheij M, Allum W et al (2016). Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 27: v38-v49.
2. Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65: 87-108.
3. Siegel RL, Miller KD, Jemal A (2018). Can-cer statistics, 2018. CA Cancer J Clin, 68: 7-30.
4. Global Burden of Disease Cancer Collabo-ration, Fitzmaurice C, Allen C, et al (2017). Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disa-bility-adjusted life-years for 32 cancer groups, 1990 to 2015:a systematic analysis for the global burden of disease study. JAMA Oncol, 3: 524-548.
5. Zhang JX, Xu Y, Gao Y, et al (2017). De-creased expression of miR-939 contrib-utes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway. Mol Cancer, 16: 18.
6. Liu L, Wang Y, Bai R, Yang K, Tian Z (2016). MiR-186 inhibited aerobic glycoly-sis in gastric cancer via HIF-1α regulation. Oncogenesis, 5: e224.
7. Bartel DP (2018). Metazoan MicroRNAs. Cell, 173: 20-51.
8. Berindan-Neagoe I, Monroig Pdel C, Pas-culli B, Calin GA (2014). MicroRNAome genome:a treasure for cancer diagnosis and therapy. CA Cancer J Clin, 64: 311-336.
9. Liu SM, Lin CH, Lu J, et al (2018). miR-596 modulates melanoma growth by regulat-ing cell survival and death. J Invest Derma-tol, 138: 911-921.
10. Wei M, Cao Y, Jia D, Zhao H, Zhang L (2019). CREPT promotes glioma cell proliferation and invasion by activating Wnt/β-catenin pathway and is a novel target of microRNA-596. Biochimie, 162: 116-124.
11. Zhang Z, Dai DQ (2019). MicroRNA-596 acts as a tumor suppressor in gastric can-cer and is upregulated by promotor de-methylation. World J Gastroenterol, 25: 1224-37.
12. Wagner AD, Syn NLX, Moehler M, et al (2017). Chemotherapy for advanced gas-tric cancer. Cochrane Database Syst Rev, 8:CD004064.
13. Ferrell BR, Temel JS, Temin S, et al (2017). Integration of palliative care into standard oncology care: American Society of Clini-cal Oncology clinical practice guideline update. J Clin Oncol, 35: 96-112.
14. Lordick F, Kang YK, Chung HC, et al (2013). Capecitabine and cisplatin with or without cetuximab for patients with pre-viously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol, 14: 490-499.
15. Satoh T, Xu RH, Chung HC, et al (2014). Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations:TyTAN—a ran-domized, phase III study. J Clin Oncol, 32: 2039-2049.
16. Endo H, Muramatsu T, Furuta M, et al (2012). Potential of tumor-suppressive miR-596 targeting LGALS3BP as a ther-apeutic agent in oral cancer. Carcinogenesis, 34: 560-569.
17. Shivapurkar N, Weiner LM, Marshall JL, et al (2014). Recurrence of early stage colon cancer predicted by expression pattern of circulating microRNAs. PLoS One, 9: e84686.
18. Anwar SL, Albat C, Krech T, et al (2013). Concordant hypermethylation of inter-genic microRNA genes in human hepa-tocellular carcinoma as new diagnostic and prognostic marker. Int J Cancer, 133: 660-670.
19. Adams JM, Cory S (2007). The Bcl-2 apop-totic switch in cancer development and therapy. Oncogene, 26: 1324-37.
20. Zhang H, Li Y, Huang Q, et al (2011). MiR-148a promotes apoptosis by targeting Bcl-2 in colorectal cancer. Cell Death Differ, 18: 1702-10.
21. Liu L, Yu X, Guo X, et al (2011). miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Mol Med Rep, 5: 753-760.
22. Li L, Yuan L, Luo J, Gao J, Guo J, Xie X (2013). MiR-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1. Clin Exp Med, 13: 109-117.
23. Sacconi A, Biagioni F, Canu V, et al (2012). miR-204 targets Bcl-2 expression and enhances responsiveness of gastric can-cer. Cell Death Dis, 3: e423.
Files
IssueVol 49 No 3 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i3.3148
Keywords
Apoptosis BCL2 proteins Correlation Gastric cancer miR-596 Proliferation

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
WANG J, YANG J, QIU J, SONG T. Regulation of miR-596 on the Apoptosis of Gastric Cancer Cells through Its Targeting Inhibition of BCL-2. Iran J Public Health. 2020;49(3):512-520.