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Anticancer Res. 2017 Oct;37(10):5425-5433.

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

Author information

1
Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju, Republic of Korea.
2
Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea.
3
Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju, Republic of Korea kdk@chosun.ac.kr.

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.

KEYWORDS:

SEMA6A; apoptosis; miR-203; oral cancer cells; tumor suppressor

PMID:
28982852
DOI:
10.21873/anticanres.11970
[Indexed for MEDLINE]

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