TSPAN31 suppresses cell proliferation in human cervical cancer through down-regulation of its antisense pairing with CDK4

Abstract

Natural antisense transcripts (NAT) are prevalent phenomena in the mammalian genome and play significant regulatory roles in gene expression. While new insights into NAT continue to be revealed, their exact function and their underlying mechanisms in human cancer remain largely unclear. We identified a NAT of CDK4, referred to TSPAN31, which inhibits CDK4 mRNA and protein expression in human cervical cancer by targeting the 3'-untranslated region (3'-UTR) of the CDK4 mRNA. Furthermore, silencing the expression of the TSPAN31 mRNA rescued the TSPAN31 3'-UTR- or the TSPAN31 full-length-induced decrease in CDK4 expression. Noteworthy, we discovered that TSPAN31, as a member of the tetraspanin family, suppressed cell proliferation by down-regulating its antisense pairing with CDK4 and decreasing retinoblastoma protein phosphorylation in human cervical cancer. Therefore, the results of the present study suggest that TSPAN31 may serve as a potential molecular target for the development of novel anti-cancer agents. SIGNIFICANCE OF THE STUDY: Natural antisense transcripts are widely found in the genome and play an important role in the growth and development of cells. TSPAN31 is natural antisense transcript, and CDK4 is an important gene in the regulation of the cell cycle. Therefore, TSPAN31 and CDK4 have great significance in the study of tumour therapeutic targets.

Keywords: CDK4; TSPAN31; human cervical cancer; natural antisense transcript.