MiR-137 Plays Tumor Suppressor Roles in Gastric Cancer Cell Lines by Targeting KLF12 and MYO1C

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2016 Jul 30

PMID 27468717

Citations 29

Authors

Yantao Du

Yichen Chen

Furong Wang

Liankun Gu

Affiliations

Soon will be listed here.

Abstract

Aberrant expression of miR-137 has been reported in many kinds of cancers, but its mechanisms seem to be diversely. In the present study, we compared the expression level of miR-137 in 18 paired gastric cancer (GC) samples and surgical margin (SM) samples by RNA extraction and quantitative real-time PCR (QRT-PCR). Then, we investigated the effects of miR-137 on cell proliferation, cell cycle, and cell migration separately by cell growth counting assay, cell cycle analysis, and transwell assay. Candidate targets of miR-137 were selected by biological information analysis from the intersection of miRDB, Pictar, and TarScan. Finally, mRNA and protein expression level of Krűppel-like factor 12 (KLF12) and Myosin 1C (MYO1C) were tested by QRT-PCR and western blotting assay, followed by the Luciferase reporter assay to investigate the direct interaction between them and miR-137. The results showed that miR-137 was down-regulated in GC samples than in SM samples. The expression level of miR-137 was significantly higher in patients without the vascular embolus than those with vascular embolus. And the overall survival time of patients with high miR-137 expression was longer than those with low miR-137 expression. Over expression of miR-137 could inhibit the cell migration, proliferation, and promote cell cycle arrest in G0/G1 stage in BGC-823 and SGC-7901 cell lines. KLF12 and MYO1C might be the candidate target genes of miR-137 with direct interactions between them and miR-137. In conclusion, miR-137 plays tumor suppressor roles in gastric cancer cell lines by targeting KLF12 and MYO1C.

Citing Articles

A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling.

Xiong S, Li S, Li Z, Song Y, Yang L, Yang H Oncogene. 2024; 43(36):2696-2707.

PMID: 39112516 DOI: 10.1038/s41388-024-03120-2.

Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential.

Liu S, Liu X, Lin X, Chen H Cells. 2023; 12(9).

PMID: 37174714 PMC: 10177130. DOI: 10.3390/cells12091314.

Significant Association of Variable Number Tandem Repeat Polymorphism rs58335419 in the MIR137 Gene With the Risk of Gastric and Colon Cancers.

Jafari P, Baghernia S, Moghanibashi M, Mohamadynejad P Br J Biomed Sci. 2022; 79:10095.

PMID: 35996520 PMC: 8915678. DOI: 10.3389/bjbs.2021.10095.

miR-2682-3p antagonizes its host lncRNA-MIR137HG by interacting with the same target FUS to regulate the progression of gastric cancer.

Du Y, Chen Y, Wu T, Fan X, Lin W, Jiang Z BMC Cancer. 2022; 22(1):689.

PMID: 35733138 PMC: 9219209. DOI: 10.1186/s12885-022-09740-9.

Long non-coding RNA p53 upregulated regulator of p53 levels (PURPL) promotes the development of gastric cancer.

Cheng Z, Hong J, Tang N, Liu F, Gu S, Feng Z Bioengineered. 2022; 13(1):1359-1376.

PMID: 35012438 PMC: 8805877. DOI: 10.1080/21655979.2021.2017588.

References

Zhang B, Liu T, Wu T, Wang Z, Rao Z, Gao J . microRNA-137 functions as a tumor suppressor in human non-small cell lung cancer by targeting SLC22A18. Int J Biol Macromol. 2014; 74:111-8. DOI: 10.1016/j.ijbiomac.2014.12.002. View

Zheng X, Dong J, Gong T, Zhang Z, Wang Y, Li Y . MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation. J Cancer Res Clin Oncol. 2014; 141(5):785-95. DOI: 10.1007/s00432-014-1847-4. View

Gillespie P . Myosin I and adaptation of mechanical transduction by the inner ear. Philos Trans R Soc Lond B Biol Sci. 2005; 359(1452):1945-51. PMC: 1693471. DOI: 10.1098/rstb.2004.1564. View

Cheng Y, Li Y, Liu D, Zhang R, Zhang J . miR-137 effects on gastric carcinogenesis are mediated by targeting Cox-2-activated PI3K/AKT signaling pathway. FEBS Lett. 2014; 588(17):3274-81. DOI: 10.1016/j.febslet.2014.07.012. View

Zhang H, Yang L, Zhu Y, Yao X, Zhang S, Dai B . Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2010; 71(3):326-31. DOI: 10.1002/pros.21246. View

Minocherhomji S, Ying S, Bjerregaard V, Bursomanno S, Aleliunaite A, Wu W . Replication stress activates DNA repair synthesis in mitosis. Nature. 2015; 528(7581):286-90. DOI: 10.1038/nature16139. View

Du Y, Liu Z, Gu L, Zhou J, Zhu B, Ji J . Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo. BMC Cancer. 2012; 12:249. PMC: 3517451. DOI: 10.1186/1471-2407-12-249. View

Oldfors C, Dios D, Linder A, Visuttijai K, Samuelson E, Karlsson S . Analysis of an independent tumor suppressor locus telomeric to Tp53 suggested Inpp5k and Myo1c as novel tumor suppressor gene candidates in this region. BMC Genet. 2015; 16:80. PMC: 4501283. DOI: 10.1186/s12863-015-0238-4. View

Xu M, Jin H, Xu C, Sun B, Mao Z, Bi W . miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 2014; 5(19):9472-83. PMC: 4253447. DOI: 10.18632/oncotarget.2418. View

10.

Kurashige J, Kamohara H, Watanabe M, Tanaka Y, Kinoshita K, Saito S . Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma. J Surg Oncol. 2012; 106(2):188-92. DOI: 10.1002/jso.23064. View

11.

Kandalam M, Beta M, Maheswari U, Swaminathan S, Krishnakumar S . Oncogenic microRNA 17-92 cluster is regulated by epithelial cell adhesion molecule and could be a potential therapeutic target in retinoblastoma. Mol Vis. 2012; 18:2279-87. PMC: 3436882. View

12.

Lee S, Chu K, Oh H, Im W, Lim J, Kim S . Let-7 microRNA inhibits the proliferation of human glioblastoma cells. J Neurooncol. 2010; 102(1):19-24. DOI: 10.1007/s11060-010-0286-6. View

13.

Liang S, He L, Zhao X, Miao Y, Gu Y, Guo C . MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer. PLoS One. 2011; 6(4):e18409. PMC: 3078939. DOI: 10.1371/journal.pone.0018409. View

14.

Fiaschetti G, Abela L, Nonoguchi N, Dubuc A, Remke M, Boro A . Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma. Br J Cancer. 2013; 110(3):636-47. PMC: 3915127. DOI: 10.1038/bjc.2013.764. View

15.

Li Y, Xu Z, Li B, Zhang Z, Luo H, Wang Y . Epigenetic silencing of miRNA-9 is correlated with promoter-proximal CpG island hypermethylation in gastric cancer in vitro and in vivo. Int J Oncol. 2014; 45(6):2576-86. DOI: 10.3892/ijo.2014.2667. View

16.

Wong T, Man O, Tsang C, Tsao S, Tsang R, Yu-Wai Chan J . MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression. J Cancer Res Clin Oncol. 2010; 137(3):415-22. PMC: 3036828. DOI: 10.1007/s00432-010-0898-4. View

17.

Li P, Ma L, Zhang Y, Ji F, Jin F . MicroRNA-137 down-regulates KIT and inhibits small cell lung cancer cell proliferation. Biomed Pharmacother. 2014; 68(1):7-12. DOI: 10.1016/j.biopha.2013.12.002. View

18.

Liu S, Cui J, Liao G, Zhang Y, Ye K, Lu T . MiR-137 regulates epithelial-mesenchymal transition in gastrointestinal stromal tumor. Tumour Biol. 2014; 35(9):9131-8. DOI: 10.1007/s13277-014-2177-5. View

19.

Ang T, Fock K . Clinical epidemiology of gastric cancer. Singapore Med J. 2015; 55(12):621-8. PMC: 4291998. DOI: 10.11622/smedj.2014174. View

20.

Ihnatovych I, Sielski N, Hofmann W . Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues. PLoS One. 2014; 9(9):e108609. PMC: 4178219. DOI: 10.1371/journal.pone.0108609. View