MiR-199b-5p Promotes Gastric Cancer Progression by Regulating HHIP Expression

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Sep 17

PMID 34532291

Citations 10

Authors

Songda Chen

Huijie Wu

Lingyu Zhu

Mengjie Jiang

Shuli Wei

Jinhua Luo

Aiqun Liu

Affiliations

Soon will be listed here.

Abstract

Objectives: Gastric cancer (GC) is one of the most common malignant tumors. More and more evidences support the role of microRNAs (miRNAs) in tumor progression. However, the role of miRNAs in human GC remains largely unknown.

Methods: Based on the published gastric cancer expression profile data, combined with bioinformatics analysis, potential miRNAs in the process of GC were screened. The expression of miR-199b-5p in GC cells and patients' plasma was detected by RT-PCR. The effects of miR-199b-5p on GC were detected by EdU proliferation assay, colony formation assay, Transwell assay and wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) related proteins. The subcutaneous tumorigenesis model and metastatic tumor model of mice were used to study its effect . Bioinformatics and Dual luciferase reporter assay were used to verify the effect of miR-199b-5p and its target gene.

Results: Through bioinformatics analysis, we screened a novel miRNA miR-199b-5p that was significantly up-regulated in GC tissue and associated with poor prognosis of GC patients. RT-PCR results showed that its expression was also up-regulated in GC cell lines and patients' plasma. MiR-199b-5p can significantly promote GC cell proliferation and migration and . Western blot showed that miR-199b-5p could promote the EMT process of GC. HHIP has been proved to be a target of miR-199b-5p, and the recovery of HHIP can weaken the effect of miR-199b-5p.

Conclusion: MiR-199b-5p may play an oncogene role in GC by targeting , suggesting that miR-199b-5p may be a potential therapeutic target for GC.

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References

Jaca A, Govender P, Locketz M, Naidoo R . The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer. J Clin Pathol. 2016; 70(4):331-356. DOI: 10.1136/jclinpath-2016-204031. View

Wei H, Li J, Shi S, Zhang L, Xiang A, Shi X . Hhip inhibits proliferation and promotes differentiation of adipocytes through suppressing hedgehog signaling pathway. Biochem Biophys Res Commun. 2019; 514(1):148-156. DOI: 10.1016/j.bbrc.2019.04.047. View

Shahi M, Zazpe I, Afzal M, Sinha S, Rebhun R, Melendez B . Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples. Tumour Biol. 2014; 36(4):2383-91. PMC: 5012430. DOI: 10.1007/s13277-014-2846-4. View

Chang L, Zhang P, Zhao D, Liu H, Wang Q, Li C . The hedgehog antagonist HHIP as a favorable prognosticator in glioblastoma. Tumour Biol. 2015; 37(3):3979-86. DOI: 10.1007/s13277-015-3442-y. View

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

Zhang H, Xing A, Ma R, Wang Y, Liu Y, Gao P . Diagnostic value of miRNA-96-5p/3p in dysplastic nodules and well-differentiated small hepatocellular carcinoma. Hepatol Res. 2015; 46(8):784-93. DOI: 10.1111/hepr.12628. View

Xu L, Duan Y, Wang P, Yin H . MiR-199b-5p promotes tumor growth and metastasis in cervical cancer by down-regulating KLK10. Biochem Biophys Res Commun. 2018; 503(2):556-563. DOI: 10.1016/j.bbrc.2018.05.165. View

Mishra S, Yadav T, Rani V . Exploring miRNA based approaches in cancer diagnostics and therapeutics. Crit Rev Oncol Hematol. 2015; 98:12-23. DOI: 10.1016/j.critrevonc.2015.10.003. View

Chen Z, Zhao G, Zhang Y, Ma Y, Ding Y, Xu N . MiR-199b-5p promotes malignant progression of osteosarcoma by regulating HER2. J BUON. 2019; 23(6):1816-1824. View

10.

Wang H, Guo Y, Mi N, Zhou L . miR-101-3p and miR-199b-5p promote cell apoptosis in oral cancer by targeting BICC1. Mol Cell Probes. 2020; 52:101567. DOI: 10.1016/j.mcp.2020.101567. View

11.

Wang B, You Z, Ren D . Target-assisted FRET signal amplification for ultrasensitive detection of microRNA. Analyst. 2019; 144(7):2304-2311. DOI: 10.1039/c8an02266f. View

12.

Buller N, Rosekrans S, Westerlund J, van den Brink G . Hedgehog signaling and maintenance of homeostasis in the intestinal epithelium. Physiology (Bethesda). 2012; 27(3):148-55. DOI: 10.1152/physiol.00003.2012. View

13.

Ikoma N, Blum M, Chiang Y, Estrella J, Roy-Chowdhuri S, Fournier K . Race Is a Risk for Lymph Node Metastasis in Patients With Gastric Cancer. Ann Surg Oncol. 2016; 24(4):960-965. DOI: 10.1245/s10434-016-5645-x. View

14.

Zhao C, Zhang Y, Popel A . Mechanistic Computational Models of MicroRNA-Mediated Signaling Networks in Human Diseases. Int J Mol Sci. 2019; 20(2). PMC: 6358731. DOI: 10.3390/ijms20020421. View

15.

Lei H, Gao Y, Xu X . LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim Biophys Sin (Shanghai). 2017; 49(7):588-597. DOI: 10.1093/abbs/gmx047. View

16.

Rupaimoole R, Slack F . MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017; 16(3):203-222. DOI: 10.1038/nrd.2016.246. View

17.

Zhang W, Liao K, Liu D . MiRNA-12129 Suppresses Cell Proliferation and Block Cell Cycle Progression by Targeting SIRT1 in GASTRIC Cancer. Technol Cancer Res Treat. 2020; 19:1533033820928144. PMC: 7281879. DOI: 10.1177/1533033820928144. View

18.

Ouyang Y, Tang Y, Fu L, Peng S, Wu W, Tan D . Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP. Cell Prolif. 2020; 53(7):e12833. PMC: 7377934. DOI: 10.1111/cpr.12833. View

19.

Li J, Ye D, Shen P, Liu X, Zhou P, Zhu G . Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway. J Exp Clin Cancer Res. 2020; 39(1):212. PMC: 7545863. DOI: 10.1186/s13046-020-01718-4. View

20.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View