Top

Published in:

01-10-2016 | Original Article

miR-137 plays tumor suppressor roles in gastric cancer cell lines by targeting KLF12 and MYO1C

Authors: Yantao Du, Yichen Chen, Furong Wang, Liankun Gu

Published in: Tumor Biology | Issue 10/2016

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.

Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singap Med J. 2014;55(12):621–8.CrossRef

Wu K, Li L, Li S. Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies. Tumour Biol. 2015;36(3):1973–81.CrossRefPubMed

Kurashige J, Kamohara H, Watanabe M, Tanaka Y, Kinoshita K, Saito S, Hiyoshi Y, Iwatsuki M, Baba Y, Baba H. Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma. J Surg Oncol. 2012;106(2):188–92.CrossRefPubMed

Gao W, Lu X, Liu L, Xu J, Feng D, Shu Y. MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol Ther. 2012;13(5):330–40.CrossRefPubMed

Zhang HL, Yang LF, Zhu Y, Yao XD, Zhang SL, Dai B, Zhu YP, Shen YJ, Shi GH, Ye DW. 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. 2011;71(3):326–31.CrossRefPubMed

Kandalam MM, Beta M, Maheswari UK, 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.PubMedPubMedCentral

Valladares-Ayerbes M, Blanco M, Haz M, Medina V, Iglesias-Díaz P, Lorenzo-Patiño MJ, Reboredo M, Santamarina I, Figueroa A, Antón-Aparicio LM, Calvo L. Prognostic impact of disseminated tumor cells and microRNA-17-92 cluster deregulation in gastrointestinal cancer. Int J Oncol. 2011;39(5):1253–64.PubMed

Li Y, Xu Z, Li B, Zhang Z, Luo H, Wang Y, Lu Z, Wu X. 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.PubMed

Fiaschetti G, Abela L, Nonoguchi N, Dubuc AM, Remke M, Boro A, Grunder E, Siler U, Ohgaki H, Taylor MD, Baumgartner M, Shalaby T, Grotzer MA. Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma. Br J Cancer. 2014;110(3):636–47.CrossRefPubMed

10.

Du Y, Liu Z, Gu L, Zhou J, Zhu BD, Ji J, Deng D. Characterization of human gastric carcinoma-related methylation of 9 miRCpG islands and repression of their expressions in vitro and in vivo. BMC Cancer. 2012;12:249.CrossRefPubMedPubMedCentral

11.

Wong TS, Man OY, Tsang CM, Tsao SW, Tsang RK, Chan JY, Ho WK, Wei WI, To VS. MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-myc expression. J Cancer Res Clin Oncol. 2011;137(3):415–22.CrossRefPubMed

12.

Lee ST, Chu K, Oh HJ, Im WS, Lim JY, Kim SK, Park CK, Jung KH, Lee SK, Kim M, Roh JK. Let-7 microRNA inhibits the proliferation of human glioblastoma cells. J Neuro-Oncol. 2011;102(1):19–24.CrossRef

13.

Liang S, He L, Zhao X, Miao Y, Gu Y, Guo C, Xue Z, Dou W, Hu F, Wu K, Nie Y, Fan D. MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer. PLoS One. 2011;6(4):e18409.CrossRefPubMedPubMedCentral

14.

Xiu Y, Liu Z, Xia S, Jin C, Yin H, Zhao W, Wu Q. MicroRNA-137 upregulation increases bladder cancer cell proliferation and invasion by targeting PAQR3. PLoS One. 2014;9(10):e109734.CrossRefPubMedPubMedCentral

15.

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. 2015;74:111–8.CrossRefPubMed

16.

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.CrossRefPubMed

17.

Liu LL, SX L, Li M, Li LZ, Fu J, Hu W, Yang YZ, Luo RZ, Zhang CZ, Yun JP. FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2. Oncotarget. 2014;5(13):5113–24.CrossRefPubMedPubMedCentral

18.

Zheng X, Dong J, Gong T, Zhang Z, Wang Y, Li Y, Shang Y, Li K, Ren G, Feng B, Li J, Tian Q, Tang S, Sun L, Li M, Zhang H, Fan D. MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation. J Cancer Res Clin Oncol. 2015;141(5):785–95.CrossRefPubMed

19.

Liu S, Cui J, Liao G, Zhang Y, Ye K, Lu T, Qi J, Wan G. MiR-137 regulates epithelial-mesenchymal transition in gastrointestinal stromal tumor. Tumour Biol. 2014;35(9):9131–8.CrossRefPubMed

20.

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.CrossRefPubMed

21.

Minocherhomji S, Ying S, Bjerregaard VA, Bursomanno S, Aleliunaite A, Wu W, Mankouri HW, Shen H, Liu Y, Hickson ID. Replication stress activates DNA repair synthesis in mitosis. Nature. 2015;528(7581):286–90.CrossRefPubMed

22.

Giefing M, Wierzbicka M, Rydzanicz M, Cegla R, Kujawski M, Szyfter K. Chromosomal gains and losses indicate oncogene and tumor suppressor gene candidates in salivary gland tumors. Neoplasma. 55(1):55–60.

23.

Xu M, Jin H, CX X, Sun B, Mao Z, Bi WZ, Wang Y. miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 2014;5(19):9472–83.CrossRefPubMedPubMedCentral

24.

Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, Shibata T. Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. Int J Cancer. 2009;125(8):1859–67.CrossRefPubMed

25.

Greenberg MJ, Ostap EM. Regulation and control of myosin-I by the motor and light chain-binding domains. Trends Cell Biol. 2013;23(2):81–9.CrossRefPubMed

26.

Gillespie PG. Myosin I and adaptation of mechanical transduction by the inner ear. Philos Trans R Soc Lond Ser B Biol Sci. 2004;359(1452):1945–51.CrossRef

27.

Hedberg Oldfors C, Dios DG, Linder A, Visuttijai K, Samuelson E, Karlsson S, Nilsson S, Behboudi A. 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.CrossRefPubMedPubMedCentral

28.

Ihnatovych I, Sielski NL, Hofmann WA. Selective expression of myosin IC isoform a in mouse and human cell lines and mouse prostate cancer tissues. PLoS One. 2014;9(9):e108609.CrossRefPubMedPubMedCentral

Title: miR-137 plays tumor suppressor roles in gastric cancer cell lines by targeting KLF12 and MYO1C
Authors: Yantao Du
Yichen Chen
Furong Wang
Liankun Gu
Publication date: 01-10-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 10/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-5199-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2016

Interactions between FGFR2 and RSK2—implications for breast cancer prognosis

Identification of MGMT promoter methylation sites correlating with gene expression and IDH1 mutation in gliomas

Prognostic value of mixed lineage kinase domain-like protein expression in the survival of patients with gastric caner

DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses

Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer

Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value

Keynote webinar | Spotlight on antibody–drug conjugates in cancer