Original Article

MiR-934 Exacerbates Malignancy of Gastric Cancer Cells by Targeting ZFP36

Abstract

Background: In order to explore new targets for the treatment of gastric cancer (GC), we investigated the regulatory mechanism of miR-934 in the malignant phenotype of gastric cancer.

Results: GC tissues and cell lines showed notably higher levels of miR-934. Overexpression of miR-934 promoted cell viability, migration and invasion, while inhibited cell apoptosis of GC cells. ZFP36 was predicted and verified to be the target of miR-934 and low protein levels of ZFP36 were observed in GC tissues. The ZFP36 protein expressions were suppressed by miR-934 overexpression, while were facilitated by miR-934 inhibition. Furthermore, the carcinogenic functions of miR-934 were partially reversed after ZFP36 overexpression. The results of in vivo experiments further demonstrated that miR-934 promoted tumor growth and repressed the protein expression of ZFP36.

Conclusion: miR-934 served as a tumor promoter in GC via targeting ZFP36, and ZFP36 overexpression could efficiently relieve malignant phenotypes caused by miR-934, which prompted an exploitable molecular target for GC treatment.

1. Johnston FM, Beckman M (2019). Updates on Management of Gastric Cancer. Curr Oncol Rep, 21: 67.
2. Siegel RL, Miller KD, Jemal A (2016). Cancer statistics, 2016. CA Cancer J Clin, 66: 7-30.
3. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F (2014). Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev, 23: 700-713.
4. Group G, Oba K, Paoletti X, et al (2013). Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer, 49: 1565-1577.
5. Zhang XY, Zhang PY (2017). Gastric cancer: somatic genetics as a guide to therapy. J Med Genet, 54: 305-312.
6. Hamashima C (2014). Current issues and future perspectives of gastric cancer screening. World J Gastroenterol, 20: 13767-13774.
7. Patel TH, Cecchini M (2020). Targeted Therapies in Advanced Gastric Cancer. Curr Treat Options Oncol, 21: 70.
8. Mishra S, Yadav T, Rani V (2016). Exploring miRNA based approaches in cancer diagnostics and therapeutics. Crit Rev Oncol Hematol, 98: 12-23.
9. Chen L, Heikkinen L, Wang C, Yang Y, Sun H, Wong G (2019). Trends in the development of miRNA bioinformatics tools. Brief Bioinform, 20: 1836-1852.
10. Bernardo BC, Ooi JY, Lin RC, McMullen JR (2015). Mirna therapeutics: a new class of drugs with potential therapeutic applications in the heart. Future Med Chem, 7: 1771-1792.
11. Lu TX, Rothenberg ME. MicroRNA (2018). J Allergy Clin Immunol, 141: 1202-1207.
12. Fabian MR, Sonenberg N (2012). The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol, 19: 586-593.
13. Rupaimoole R, Slack FJ (2017). MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov, 16: 203-222.
14. Wang C, Huang Y, Zhang J, Fang Y (2020). miRNA-339-5p suppresses the malignant development of gastric cancer via targeting ALKBH1. Exp Mol Pathol, 115: 104449.
15. Hu X, Zhang M, Miao J, Wang X, Huang C (2018). miRNA-4317 suppresses human gastric cancer cell proliferation by targeting ZNF322. Cell Biol Int, 42: 923-930.
16. Lin J, Shen J, Yue H, Cao Z (2019). miRNA1835p.1 promotes the migration and invasion of gastric cancer AGS cells by targeting TPM1. Oncol Rep, 42: 2371-2381.
17. Liu B, Li J, Cairns MJ (2014). Identifying miRNAs, targets and functions. Brief Bioinform, 15: 1-19.
18. Zhao YB, Zhao XY, Jia J, Liu J, Xu JL, Li N (2021). Up-regulation of miR-934 serves as an independent prognostic factor for lung cancer and promotes proliferation, migration and invasion of non-small cell lung cancer cells. J Biol Regul Homeost Agents, 35: 315-322.
19. Zhao S, Mi Y, Guan B, et al (2020). Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol, 13: 156.
20. Lu Y, Hu X, Yang X (2021). miR-934 promotes breast cancer metastasis by regulation of PTEN and epithelial-mesenchymal transition. Tissue Cell, 71: 101581.
21. Liu W, Ma L, Zhang J (2021). MicroRNA-934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf-related protein 2. Exp Ther Med, 22: 1041.
22. Jin Y, Weng Y, Wang Y, et al (2020). miR-934 as a Prognostic Marker Facilitates Cell Proliferation and Migration of Pancreatic Tumor by Targeting PROX1. Onco Targets Ther, 13: 3389-3399.
23. Hu Y, Zhang Q, Cui J, et al (2019). Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L. Eur Rev Med Pharmacol Sci, 23: 5595-5602.
24. Poh AR, O'Donoghue RJ, Ernst M, Putoczki TL (2016). Mouse models for gastric cancer: Matching models to biological questions. J Gastroenterol Hepatol, 31: 1257-1272.
25. Chen W, Chen M, Zhao Z, et al (2020). ZFP36 Binds With PRC1 to Inhibit Tumor Growth and Increase 5-Fu Chemosensitivity of Hepatocellular Carcinoma. Front Mol Biosci, 7: 126.
26. Selmi T, Martello A, Vignudelli T, et al (2012). ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways. Cell Cycle, 11: 1977-1987.
27. Xia W, Liu Y, Du Y, Cheng T, Hu X, Li X (2020). MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36. Onco Targets Ther, 13: 769-782.
28. Pan QH, Fan YH, Wang YZ, Li DM, Hu CE, Li RX (2020). Long noncoding RNA NNT-AS1 functions as an oncogene in breast cancer via repressing ZFP36 expression. J Biol Regul Homeost Agents, 34: 795-805.
29. Shin VY, Chu KM (2014). miRNA as potential biomarkers and therapeutic targets for gastric cancer. World J Gastroenterol, 20: 10432-10439.
30. Castilla MA, Lopez-Garcia MA, Atienza MR, et al (2014). VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer. Endocr Relat Cancer, 21: 587-599.
31. Saad MA, Kuo SZ, Rahimy E, et al (2015). Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma. Mol Cancer, 14: 181.
32. Yan H, Ren S, Lin Q, et al (2019). Inhibition of UBE2N-dependent CDK6 protein degradation by miR-934 promotes human bladder cancer cell growth. FASEB J, 33: 12112-12123.
33. Mao Y, Lv M, Cao W, et al (2020). Circular RNA 000554 represses epithelial-mesenchymal transition in breast cancer by regulating microRNA-182/ZFP36 axis. FASEB J, 34: 11405-11420.
34. Fang S, Zhao Y, Hu X (2020). LncRNA ADAMTS9-AS1 Restrains the Aggressive Traits of Breast Carcinoma Cells via Sponging miR-513a-5p. Cancer Manag Res, 12: 10693-10703.
35. Chen W, Di Z, Chen Z, et al (2021). NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2-associated ETFA. J Cell Mol Med, 25: 9038-9050.
36. Wang H, Chen Y, Guo J, et al (2018). Dysregulation of tristetraprolin and human antigen R promotes gastric cancer progressions partly by upregulation of the high-mobility group box 1. Sci Rep, 8: 7080.
37. Guo J, Qu H, Shan T, Chen Y, Chen Y, Xia J (2018). Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity. Mol Cells, 41: 653-664.
Files
IssueVol 52 No 8 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v52i8.13411
Keywords
Gastric cancer Microrna-934 Cell growth Cell metastasis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Pan Z, Yun H, Xiao Y, Tong F, Liu G, Zhang G, Han J. MiR-934 Exacerbates Malignancy of Gastric Cancer Cells by Targeting ZFP36. Iran J Public Health. 2023;52(8):1720-1729.