TSPAN31 is a critical regulator on transduction of survival and apoptotic signals in hepatocellular carcinoma cells.

Tetraspanins are commonly believed to act as 'molecular facilitators', not directly involved in signal transduction. Tetraspanin 31 (TSPAN31), recently discovered to be linked to cancer, has not yet been studied in hepatocellular carcinoma (HCC). Here, we show that TSPAN31 is the natural antisense transcript of cyclin dependent kinase 4 (CDK4), and regulates the expression of CDK4 mRNA and protein. Target analysis indicates that miR-135b can directly regulate TSPAN31 expression. miR-135b-induced TSPAN31 silencing increases CDK4 protein levels. Interestingly, p53 negatively regulates TSPAN31 expression. siRNA-induced TSPAN31 knockdown reduces the expression of Akt signaling pathway components phosphorylated Akt, p-GSK3β and β-catenin, and restrains β-catenin migration to cell nucleus. TSPAN31 knockdown also significantly inhibits HCC cell invasion and migration. These findings thus point to TSPAN31 as a novel regulator in transduction of intracellular survival and apoptotic signals.