Overexpression of long non-coding RNA GASL1 induces apoptosis and G0/G1 cell cycle arrest in human oral cancer cells.

Abstract

Oral cancer is one of the commonly reported malignancies of the human oral cavity and pharynx. It accounts for a significant level of cancer-based mortality across the globe. Long non-coding RNAs (lncRNAs) are emerging as important study targets in cancer therapy. The present study aimed to characterize the role of lncRNA GASL1 in regulating the growth, migration, and invasion of human oral cancer cells. The qRT-PCR showed significant (P<0.05) upregulation of GASL1 in oral cancer cells. Overexpression of GASL1 led to the loss of viability of HN6 oral cancer cells by inducing apoptosis which was associated with upregulation of Bax and downregulation of Bcl-2. The apoptotic cell percentage increased from 2. 81% in control to 25.89% upon GASL1 overexpression. Cell cycle analysis showed that overexpression of GASL1 increased the G1 cells from 35.19% in control to 84.52% upon GASL1 overexpression indicative of G0/G1 cell cycle arrest. Cell cycle arrest was also accompanied by inhibition of cyclin D1 and CDK4 protein expression. Wound healing and transwell assays showed that overexpression of GASL1 significantly (P<0.05) inhibited the migration and invasion of HN6 oral cancer cells. The invasion of the HN6 oral cancer cells was found to be decreased by more than 70%. Finally, the results of in vivo study revealed that GASL1 overexpression inhibits the xenografted tumor growth in vivo. Thus, the results are thus suggestive of the tumor-suppressive molecular role of GASL1 in oral cancer cells.