TSPAN 31 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 TSPAN 31 is the natural antisense transcript of cyclin dependent kinase 4 (CDK4), and regulates the expression of CDK 4 mRNA and protein. Target analysis indicates that miR‐135b can directly regulate TSPAN 31 expression. miR‐135b‐induced TSPAN 31 silencing increases CDK 4 protein levels. Interestingly, p53 negatively regulates TSPAN 31 expression. si RNA ‐induced TSPAN 31 knockdown reduces the expression of Akt signaling pathway components phosphorylated Akt, p‐ GSK 3β and β‐catenin, and restrains β‐catenin migration to cell nucleus. TSPAN 31 knockdown also significantly inhibits HCC cell invasion and migration. These findings thus point to TSPAN 31 as a novel regulator in transduction of intracellular survival and apoptotic signals.