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.

中文翻译：

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TSPAN31通过下调与CDK4的反义配对来抑制人宫颈癌中的细胞增殖

天然反义转录本（NAT）是哺乳动物基因组中普遍存在的现象，并且在基因表达中起着重要的调节作用。尽管人们继续揭示出有关NAT的新见解，但它们在人类癌症中的确切功能及其潜在机制仍不清楚。我们确定了CDK4的NAT，称为TSPAN31，它通过靶向CDK4 mRNA的3'-非翻译区（3'-UTR）抑制人宫颈癌中的CDK4 mRNA和蛋白质表达。此外，沉默TSPAN31 mRNA的表达可以挽救TSPAN31 3'-UTR-或TSPAN31全长诱导的CDK4表达下降。值得注意的是，我们发现TSPAN31作为四跨膜蛋白家族的成员，通过下调其与CDK4的反义配对并减少人宫颈癌中的成视网膜细胞瘤蛋白磷酸化来抑制细胞增殖。因此，本研究的结果表明，TSPAN31可能作为新型抗癌药开发的潜在分子靶标。