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MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence

机译:MicroRNA-212通过抑制SIRT1负调节前列腺癌中饥饿诱导的自噬并且是血管生成和细胞衰老的调节剂

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摘要

Among a number of non-coding RNAs, role of microRNAs (miRNAs) in cancer cell proliferation, cancer initiation, development and metastasis have been extensively studied and miRNA based therapeutic approaches are being pursued. Prostate cancer (PCa) is a major health concern and several deregulated miRNAs have been described in PCa. miR-212 is differentially modulated in multiple cancers however its function remains elusive. In this study, we found that miR-212 is downregulated in PCa tissues when compared with benign adjacent regions (n = 40). Also, we observed reduced levels of circulatory miR-212 in serum from PCa patients (n = 40) when compared with healthy controls (n = 32). Elucidating the functional role of miR-212, we demonstrate that miR-212 negatively modulates starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1). Overexpression of miR-212 also leads to inhibition of angiogenesis and cellular senescence. In conclusion, our study indicates a functional role of miR-212 in PCa and suggests the development of miR-212 based therapies.
机译:在许多非编码RNA中,已经广泛研究了microRNA(miRNA)在癌细胞增殖,癌症起始,发展和转移中的作用,并且正在寻求基于miRNA的治疗方法。前列腺癌(PCa)是一个主要的健康问题,在PCa中已经描述了几种失控的miRNA。 miR-212在多种癌症中受到差异调节,但其功能仍然难以捉摸。在这项研究中,我们发现与良性邻近区域(n = 40)相比,miR-212在PCa组织中被下调。此外,与健康对照组(n = 32)相比,我们观察到PCa患者(n = 40)血清中循环miR-​​212水平降低。阐明了miR-212的功能作用,我们证明了miR-212通过靶向沉默调节蛋白1(SIRT1)负调控PCa细胞中饥饿诱导的自噬。 miR-212的过表达也导致血管生成和细胞衰老的抑制。总之,我们的研究表明了miR-212在PCa中的功能作用,并提出了基于miR-212的疗法的发展。

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