Role of Gα13 induced microRNAs in oncogenesis and metastasis

Abstract

G alpha 13 (Gα13), a heterotrimeric G–protein, signals through GPCRs. It is a potent regulator of cancer cell invasion, migration and metastasis in many cancer types. MicroRNAs (miRNAs), small non-coding RNAs, bind to mRNA of target genes and inhibit their protein expression and function. Recent reports show that specific miRNAs regulate cell invasion in prostate and breast cancers by inhibiting Gα13 expression and therefore its signaling. This exploratory study focuses on finding miRNAs regulated by Gα13 in head and neck cancers. To this end, a screen for expression of a set of miRNAs important in cancer biology was conducted in presence/absence of Gα13 using real time PCRs (RT-PCRs). To determine probable target genes, online miRNA-gene target prediction tool, miRSystem.cgm was used. Gα13 mRNA and protein expression was studied using western blotting and RT-PCR respectively. Knockdown of Gα13 in TM38 and TM17 cells using specific Sh-RNAs targeting Gα13 showed consistent and significant downregulation of miR-132/212 and miR-424. Using miRSystem.cgm, we identified YAP1 (Yes Associated Protein 1) as a potential target gene for both miR-212 and miR-424. The preliminary screen for YAP1 protein expression showed an increase upon knockdown of Gα13 in head and neck cancer cell lines. YAP1 is known to have critical role in tumor biology. Hence, we believe validating miR-132/212/424’s effect on YAP1 could provide valuable information on the role of Gα13 in regulating YAP1 signaling pathway via these specific miRNAs and its impact on the biology of cancers.