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Androgen receptor regulates ASS1P3/miR-34a-5p/ASS1 signaling to promote renal cell carcinoma cell growth

机译:雄激素受体调节ASS1P3 / miR-34a-5p / ASS1信号传导促进肾癌细胞的生长

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摘要

Recent studies have demonstrated that the androgen receptor (AR) could play important roles to promote renal cell carcinoma (RCC) cell proliferation, and other studies have also indicated that suppressing the argininosuccinate synthase 1 (ASS1) could promote proliferation of various tumors. The potential of AR promoting cell proliferation in RCC via altering ASS1, however, remains unclear. Here we found that the expression of ASS1 was lower in RCC tissues than in adjacent normal renal tissues, and a lower ASS1 expression was linked to a worse prognosis in RCC patients. Mechanism dissection showed that AR could decrease ASS1 expression to promote RCC cell proliferation via ASS1P3, a pseudogene of ASS1. The results of RIP assay and AGO2 assay revealed that AR could bind ASS1P3 to increase RCC cell proliferation via altering miR-34a-5p function, which could bind to the 3′UTR of ASS1 to suppress its protein expression. ASS1P3 could function as a miRNA decoy for miR-34a-5p to regulate ASS1 in RCC. Preclinical study also supports the in vitro data. Together, these results demonstrated that ASS1P3 could function as a competing endogenous RNA to suppress RCC cell progression, and targeting this newly identified AR-mediated ASS1P3/miR-34a-5p/ASS1 signaling might help in blocking proliferation.
机译:最近的研究表明,雄激素受体(AR)可能在促进肾细胞癌(RCC)细胞增殖中起重要作用,其他研究也表明抑制精氨酸琥珀酸合酶1(ASS1)可以促进各种肿瘤的增殖。然而,AR通过改变ASS1促进RCC中细胞增殖的潜力尚不清楚。在这里,我们发现ASS1在RCC组织中的表达低于相邻的正常肾脏组织,而ASS1的较低表达与RCC患者的预后较差有关。机制剖析显示,AR可能通过ASS1的假基因ASS1P3降低ASS1表达,从而促进RCC细胞增殖。 RIP分析和AGO2分析的结果表明,AR可以通过改变miR-34a-5p的功能与ASS1P3结合,从而增加RCC细胞的增殖,并与ASS1的3'UTR结合,从而抑制其蛋白表达。 ASS1P3可以作为miR-34a-5p的miRNA诱饵来调节RCC中的ASS1。临床前研究也支持体外数据。总之,这些结果表明ASS1P3可以作为竞争性内源RNA来抑制RCC细胞进程,并且靶向这种新近鉴定的AR介导的ASS1P3 / miR-34a-5p / ASS1信号传导可能有助于阻止增殖。

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