lncRNA HCG11 regulates cell progression by targeting miR-543 and regulating AKT/mTOR pathway in prostate cancer
lncRNA HCG11 regulates cell progression by targeting miR-543 and regulating AKT/mTOR pathway in prostate cancer
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DOI：
10.1002/cbin.11194
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发表时间：
2019-08-26
影响因子：
3.9
通讯作者：
Ma, Yong-Liang
中科院分区：
文献类型：
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作者：
Wang, Yan-Chao;He, Wen-Yan;Ma, Yong-Liang
前列腺癌（PCa）是一种世界性的常见癌症，多发生于50岁以上的男性。越来越多的证据表明，长链非编码RNA/microRNA （lncRNA/miRNA）轴在包括PCa在内的癌症的细胞进展中起着关键作用。然而，前列腺癌的发病机制尚未完全明确。本研究采用实时定量聚合酶链反应检测HCG11和miR-543的表达。Western blot检测增殖细胞核抗原、裂解caspase 3 （cle-caspase 3）、N-cadherin、E-cadherin、GAPDH、P-AKT、AKT、p-mTOR、mTOR的蛋白表达。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）、transwell侵袭和transwell迁移法分别检测细胞增殖、侵袭和迁移。在PCa细胞和异种移植小鼠模型中证实了lncRNA HCG11的功能和机制。荧光素酶检测显示miR-543是HCG11的靶miRNA。进一步的研究表明，HCG11过表达抑制细胞增殖、侵袭和迁移，同时通过调节miR-543的表达诱导细胞凋亡。不仅如此，lncRNA HCG11还通过抑制PI3K/AKT信号通路抑制PCa的进展。我们的数据显示，hgc11过表达通过下调miR-543的表达抑制PI3K/AKT信号通路，导致PCa细胞生长受到抑制。这一发现证实了前列腺癌的一个新的调控网络，并为前列腺癌的治疗提供了新的靶点。
Prostate cancer (PCa) is a common cancer worldwide, which mostly occurs in males over the age of 50. Accumulating evidence have determined that long non-coding RNA/microRNA (lncRNA/miRNA) axis plays a critical role in cell progression of cancers, including PCa. However, the pathogenesis of PCa has not been fully indicated. In this study, quantitative real-time polymerase chain reaction was used to detect the expression of HCG11 and miR-543. Western blot was applied to measure the protein expression of proliferating cell nuclear antigen, cleavage-caspase 3 (cle-caspase 3), N-cadherin, E-cadherin, GAPDH, P-AKT, AKT, p-mTOR, and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell invasion, and transwell migration assay were used to detect cell proliferation, invasion, and migration, respectively. The function and mechanism of lncRNA HCG11 were confirmed in PCa cell and xenograft mice models. Luciferase assay indicated that miR-543 was a target miRNA of HCG11. Further investigation revealed that overexpression of HCG11 inhibited cell proliferation, invasion, and migration, whereas induced cell apoptosis by regulating miR-543 expression in vitro and in vivo. More than that, lncRNA HCG11 inhibited phosphoinositide-3 kinase/protein kinaseB (PI3K/AKT) signaling pathway to suppress PCa progression. Our data showed the overexpression of HGC11-inhibited PI3K/AKT signaling pathway by downregulating miR-543 expression, resulting in the suppression of cell growth in PCa. This finding proved a new regulatory network in PCa and provided a novel therapeutic target of PCa.