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MicroRNA‐4286 promotes cell proliferation migration and invasion via PTEN regulation of the PI3K/Akt pathway in non‐small cell lung cancer

机译:MicroRNA-4286通过PTEN调节非小细胞肺癌中PI3K / Akt途径促进细胞增殖迁移和侵袭

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摘要

It is well‐known that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor which negatively regulates PI3K/AKT signaling and is activated widely in non‐small cell lung cancers (NSCLC). However, genetic alterations in PTEN genes are rare, suggesting an undefined mechanism(s) for their suppression. Notably, growing evidence indicates that PTEN can be regulated by microRNAs involved in cancer progression. In this study, we discover that the miR‐4286 is overexpressed in NSCLC and negatively regulates the expression of PTEN. Furthermore, we found that miR‐4286 reduces PTEN expression by directly binding to PTEN 3′‐untranslated region (UTR), thereby inhibiting NSCLC cell proliferation and mobility. Moreover, mechanistic investigations revealed that miR‐4286 overexpression was a result of PTEN‐mediated activation of the PI3K/AKT pathway. Taken together, our findings elucidate that miR‐4286 promotes the tumorigenesis of NSCLC by interacting with PTEN. This miR‐4286‐mediated upregulation of PTEN might lead to new therapeutic strategies for NSCLC.
机译:众所周知,在10号染色体(PTEN)上缺失的磷酸酶和张力蛋白同源物是一种肿瘤抑制因子,它负调节PI3K / AKT信号传导,并在非小细胞肺癌(NSCLC)中被广泛激活。但是,PTEN基因的遗传改变很少见,提示其抑制作用的机制尚不确定。值得注意的是,越来越多的证据表明PTEN可以由参与癌症进展的microRNA调控。在这项研究中,我们发现miR-4286在NSCLC中过表达并且对PTEN的表达负调控。此外,我们发现miR-4286通过直接结合PTEN 3'-非翻译区(UTR)来降低PTEN表达,从而抑制NSCLC细胞增殖和迁移。此外,机理研究表明,miR-4286过表达是PTEN介导的PI3K / AKT途径活化的结果。综上所述,我们的发现阐明了miR-4286通过与PTEN相互作用促进了NSCLC的肿瘤发生。这种miR-4286介导的PTEN上调可能会导致NSCLC的新治疗策略。

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