MicroRNA-193b Acts As a Tumor Suppressor Gene in Human Esophageal Squamous Cell Carcinoma Via Target Regulation of KRAS

Overview

Journal Oncol Lett

Specialty Oncology

Date 2019 Mar 19

PMID 30881513

Citations 11

Authors

Min Kang

Yan Li

Shengtao Zhu

Shutian Zhang

Shuilong Guo

Peng Li

Affiliations

Soon will be listed here.

Abstract

In recent years, microRNA-193b (miR-193b) is regarded as a tumor suppressor in the development and progression of various cancers. Several studies have indicated that KRAS could be regulated by miR-193b in pancreatic cancer cells. However, the function of miR-193b in human esophageal squamous cell carcinoma has not been explored intensively thus far. Herein, the relationship between miR-193b and KRAS was mainly explored in esophageal squamous cell carcinoma cells. In the present study, the expression levels of miR-193b and KRAS were assessed in both human esophageal cancer cells and tissues. The direct regulatory relationship between miR-193b and KRAS was evaluated using dual-luciferase assay. The effect of miR-193b overexpression and inhibitor on cell proliferation, migration/invasion, and apoptosis was further detected herein. Our results indicated that the expression of miR-193b was significantly lower in human esophageal cancer tissues than paracancerous tissues. The expression level of miR-193b/KRAS was stage-dependent in human esophageal cancers. KRAS was indicated as the direct target of miR-193b, and upregulation of miR-193b increased the percentage of cell apoptosis, and suppressed cell proliferation as well as cell migration/invasion via direct regulation of KRAS. Therefore, our study indicated that miR-193b plays an important role in the development and progression of human esophageal squamous cell carcinoma, which may become a novel target in the treatment of human esophageal squamous cell carcinoma in the future.

Citing Articles

Deciphering the roles of non-coding RNAs in liposarcoma development: Challenges and opportunities for translational therapeutic advances.

Chong Z, Ho W, Yeap S Noncoding RNA Res. 2024; 11:73-90.

PMID: 39736850 PMC: 11683247. DOI: 10.1016/j.ncrna.2024.11.005.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Wei Q, Jin F, Wang Z, Li B, Cao W, Sun Z World J Gastroenterol. 2024; 30(11):1497-1523.

PMID: 38617454 PMC: 11008420. DOI: 10.3748/wjg.v30.i11.1497.

Pronounced Enhancement in Radiosensitization of Esophagus Cancer Cultivated in Docosahexaenoic Acid via the γ Activation.

Yang Y, Xu Y, Zhao C, Zhang L, Nuerbol A, Wang L Front Med (Lausanne). 2023; 9:922228.

PMID: 37153924 PMC: 10155814. DOI: 10.3389/fmed.2022.922228.

MIMRDA: A Method Incorporating the miRNA and mRNA Expression Profiles for Predicting miRNA-Disease Associations to Identify Key miRNAs (microRNAs).

Li X, Ai H, Li B, Zhang C, Meng F, Ai Y Front Genet. 2022; 13:825318.

PMID: 35154284 PMC: 8829120. DOI: 10.3389/fgene.2022.825318.

Emerging role of non-coding RNAs in the regulation of KRAS.

Ghafouri-Fard S, Shirvani-Farsani Z, Hussen B, Taheri M, Jalili Khoshnoud R Cancer Cell Int. 2022; 22(1):68.

PMID: 35139853 PMC: 8827276. DOI: 10.1186/s12935-022-02486-1.

References

Li X, Yan P, Shao Z . Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer. Oncogene. 2009; 28(44):3937-48. DOI: 10.1038/onc.2009.245. View

Rauhala H, Jalava S, Isotalo J, Bracken H, Lehmusvaara S, Tammela T . miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer. Int J Cancer. 2010; 127(6):1363-72. DOI: 10.1002/ijc.25162. View

Chen J, Feilotter H, Pare G, Zhang X, Pemberton J, Garady C . MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. Am J Pathol. 2010; 176(5):2520-9. PMC: 2861116. DOI: 10.2353/ajpath.2010.091061. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Liu Y, Wu T, Song J, Chen X, Zhang Y, Wan Y . A mutant screening method by critical annealing temperature-PCR for site-directed mutagenesis. BMC Biotechnol. 2013; 13:21. PMC: 3606131. DOI: 10.1186/1472-6750-13-21. View

Liu P, Chen S, Li X, Qin L, Huang K, Wang L . Low immunogenicity of neural progenitor cells differentiated from induced pluripotent stem cells derived from less immunogenic somatic cells. PLoS One. 2013; 8(7):e69617. PMC: 3724937. DOI: 10.1371/journal.pone.0069617. View

Gastaldi C, Bertero T, Xu N, Bourget-Ponzio I, Lebrigand K, Fourre S . miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma. Carcinogenesis. 2013; 35(5):1110-20. DOI: 10.1093/carcin/bgt490. View

Napier K, Scheerer M, Misra S . Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol. 2014; 6(5):112-20. PMC: 4021327. DOI: 10.4251/wjgo.v6.i5.112. View

Tutar L, Tutar E, Tutar Y . MicroRNAs and cancer; an overview. Curr Pharm Biotechnol. 2014; 15(5):430-7. DOI: 10.2174/1389201015666140519095304. View

10.

Liu P, Zhang Y, Chen S, Cai J, Pei D . Application of iPS cells in dental bioengineering and beyond. Stem Cell Rev Rep. 2014; 10(5):663-70. DOI: 10.1007/s12015-014-9531-2. View

11.

Li J, Kong F, Wu K, Song K, He J, Sun W . miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer. Mol Med Rep. 2014; 10(5):2613-20. DOI: 10.3892/mmr.2014.2558. View

12.

Hummel R, Sie C, Watson D, Wang T, Ansar A, Michael M . MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines. World J Gastroenterol. 2014; 20(40):14904-12. PMC: 4209553. DOI: 10.3748/wjg.v20.i40.14904. View

13.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

14.

Mitra A, Chiang C, Tiwari P, Tomar S, Watters K, Peter M . Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis. Oncogene. 2015; 34(48):5923-32. PMC: 4580483. DOI: 10.1038/onc.2015.43. View

15.

Jin X, Sun Y, Yang H, Li J, Yu S, Chang X . Deregulation of the MiR-193b-KRAS Axis Contributes to Impaired Cell Growth in Pancreatic Cancer. PLoS One. 2015; 10(4):e0125515. PMC: 4408116. DOI: 10.1371/journal.pone.0125515. View

16.

Wen S, Zhang Y, Li Y, Liu Z, Lv H, Li Z . Characterization and effects of miR-21 expression in esophageal cancer. Genet Mol Res. 2015; 14(3):8810-8. DOI: 10.4238/2015.August.3.4. View

17.

Liu P, Cai J, Dong D, Chen Y, Liu X, Wang Y . Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells. PLoS One. 2015; 10(10):e0141346. PMC: 4619695. DOI: 10.1371/journal.pone.0141346. View

18.

Liu P, Feng Y, Dong D, Liu X, Chen Y, Wang Y . Enhanced renoprotective effect of IGF-1 modified human umbilical cord-derived mesenchymal stem cells on gentamicin-induced acute kidney injury. Sci Rep. 2016; 6:20287. PMC: 4735814. DOI: 10.1038/srep20287. View

19.

Nyhan M, ODonovan T, Boersma A, Wiemer E, McKenna S . MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells. BMC Cancer. 2016; 16:101. PMC: 4754993. DOI: 10.1186/s12885-016-2123-6. View

20.

Gupta B, Kumar N . Worldwide incidence, mortality and time trends for cancer of the oesophagus. Eur J Cancer Prev. 2016; 26(2):107-118. DOI: 10.1097/CEJ.0000000000000249. View