Suppression of Oral Carcinoma Oncogenic Activity by microRNA-203 via Down-regulation of SEMA6A.

Abstract

BACKGROUND/AIM:

The purpose of this study was to elucidate the molecular mechanism underlying regulation of semaphorin-6A (SEMA6A) involving microRNA-203 (miR-203) as a tumor suppressor in YD-38 human oral cancer cells.

MATERIALS AND METHODS:

miRNA arrays, polymerase chain reaction analyses, MTT assays, immunoblotting, and luciferase assays were carried out in YD-38 cells.

RESULTS:

MiRNA microarray results showed that expression of miR-203 was significantly down-regulated in YD-38 cells compared to normal human oral keratinocytes. The viability of YD-38 cells was reduced by miR-203 in time- and dose-dependent manners. Overexpression of miR-203 increased the nuclear condensation of YD-38 cells and activated the apoptotic signaling pathway by up-regulating pro-apoptotic factors, such as BCL-2-associated X protein (BAX) and BCL-2 homologous antagonist killer (BAK), and the active forms of caspase-9, caspase-3, and poly-(ADP-ribose)-polymerase (PARP). Furthermore, target gene array analyses revealed that the expression of class 6 semaphorin A (SEMA6A) was down-regulated by miR-203 in YD-38 cells. Both the mRNA and protein levels of SEMA6A were reduced in YD-38 cells transfected with miR-203. Luciferase activity assay confirmed that miR-203 directly targets the SEMA6A 3'-untranslated region to suppress gene expression.

CONCLUSION:

Our results indicate that miR-203 induces the apoptosis of YD-38 human oral cancer cells by directly targeting SEMA6A, suggesting its potential application in anticancer therapeutics.

• Authors: Hyoung-Sup Lim, Chun Sung Kim, Jae-Sung Kim, Sun-Kyoung Yu, Dae-San Go, Seul Ah Lee, Sung Min Moon, Hong Sung Chun, Su Gwan Kim, DO Kyung Kim
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 10 Pg. 5425-5433 (10 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 28982852 (Publication Type: Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• 3' Untranslated Regions
• Apoptosis Regulatory Proteins
• MIRN203 microRNA, human
• MicroRNAs
• RNA, Messenger
• SEMA6A protein, human
• Semaphorins

Topics

• 3' Untranslated Regions
• Apoptosis
• Apoptosis Regulatory Proteins (metabolism)
• Binding Sites
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Down-Regulation
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• Mouth Neoplasms (genetics, metabolism, pathology)
• Oncogenes
• RNA, Messenger (genetics, metabolism)
• Semaphorins (genetics, metabolism)
• Signal Transduction
• Time Factors
• Transfection