Gαi1 Promoted Proliferation, Migration and Invasion via Activating the Akt-mTOR/Erk-MAPK Signaling Pathway in Renal Cell Carcinoma

Background: Renal cell carcinoma (RCC) accounts for about 2-3% of all adult malignancies. G protein alpha inhibitory subunit 1 (G alpha i1) plays a key role in mediating PI3K-Akt signaling upon activation of receptor tyrosine kinases (RTKs). However, little is known about its expression, regulation and biological function in RCC. Methods: Gail expression in RCC tissues and cells was detected by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC). The effect of Gail silence on cell proliferation and apoptosis of 786-O and ACHN cells was detected by CCK-8 assay and flow cytometry. Wound-healing assay and Transwell assays were used to detect the cell invasion in RCC cells. The expression of CDK4, cyclin D1, MMP-2, MMP-9, Bax, Bc1-2, p/t-Akt, p/t-S6 and p/t-Erk was detected by Western blot and qRT-PCR. Furthermore, a nude mouse subcutaneous xenograft model was used to further evaluate the potential effects of Gail in vivo. Results: In the present study, our data showed that G alpha i1 expression was dramatically increased in RCC tissues compared with normal renal tissues. In addition, knocking down the expression of Gail subsequently inhibited proliferation, migration and invasion of RCC cells in vivo and vitro. Furthermore, the expression of CDK4, cyclin D1, MMP-2 and MMP-9 was significantly reduced upon G alpha i1 inhibition. G alpha i1 positively regulates the activation of the mTOR and Erk pathways. Conclusion: In conclusion, this study reveals G alpha i1 promoted proliferation via activating the Akt-mTOR and Erk-MAPK signaling pathways in RCC, and Gail may be a therapeutic and prognostic target for RCC.

Automated summary

The study showed that G alpha inhibitory subunit 1 (G alpha i1) expression is significantly increased in renal cell carcinoma (RCC) tissues, and silencing Gail inhibits proliferation and invasion of RCC cells. Additionally, G alpha i1 regulates the expression of proliferation-related proteins in RCC cells.