miR-203 downregulates Yes-1 and suppresses oncogenic activity in human oral cancer cells

• Published in: Journal of bioscience and bioengineering 2015-10, Vol.120 (4), p.351-358
• Main Authors: Lee, Seul-Ah, Kim, Jae-Sung, Park, Sun-Young, Kim, Heung-Joong, Yu, Sun-Kyoung, Kim, Chun Sung, Chun, Hong Sung, Kim, Jeongsun, Park, Jong-Tae, Go, Daesan, Kim, Do Kyung
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Apoptosis; Apoptosis - genetics; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Gene Expression Regulation, Neoplastic - genetics; Genes, Tumor Suppressor; Humans; MicroRNAs - genetics; MicroRNAs - therapeutic use; miR-203; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Oligonucleotide Array Sequence Analysis; Oral cancer cells; Proto-Oncogene Proteins c-yes - biosynthesis; Proto-Oncogene Proteins c-yes - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Transfection; Tumor suppressor; Yes-1
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2015.02.002

The purpose of this study was to elucidate the molecular mechanisms of microRNA-203 (miR-203) as a tumor suppressor in KB human oral cancer cells. MicroRNA microarray results showed that the expression of miR-203 was significantly down-regulated in KB cells compared with normal human oral keratinocytes. The viability of KB cells was decreased by miR-203 in the time- and dose-dependent manners. In addition, over-expressed miR-203 not only increased the nuclear condensation but also significantly increased the apoptotic population of KB cells. These results indicated that the over-expression of miR-203 induced apoptosis of KB cells. Furthermore, the target gene array analyses revealed that the expression of Yes-1, a member of the Src family kinases (SFKs), was significantly down-regulated by miR-203 in KB cells. Moreover, both the mRNA and protein levels of Yes-1 were strongly reduced in KB cells transfected with miR-203. Therefore, these results indicated that Yes-1 is predicted to be a potential target gene of miR-203. Through a luciferase activity assay, miR-203 was confirmed to directly targets the Yes-1 3′ untranslated region (UTR) to suppress gene expression. Therefore, our findings indicate that miR-203 induces the apoptosis of KB cells by directly targeting Yes-1, suggesting its application in anti-cancer therapeutics.