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HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability.
Cell Biochemistry and Biophysics ( IF 2.6 ) Pub Date : 2020-09-08 , DOI: 10.1007/s12013-020-00939-w
Xiaohui Yu 1 , Yujiao Li 1 , Yumei Ding 1 , Hong Zhang 1 , Ning Ding 1 , Ming Lu 1
Affiliation  

The human antigen R (HuR) could play an essential role in stabilizing the mRNAs of many tumor-associated genes. Little research is performed to investigate the relevant mechanism mediated by HuR to promote the progress of ovarian cancer. The Cancer Genome Atlas (TCGA) dataset was retrieved to calculate the correlation between HuR and translocase of inner mitochondrial membrane 44 (TIMM44) expression. HuR expression plasmid, TIMM44 expression plasmid, siRNA HuR, and TIMM44 siRNAs were further transfected into A2780 and SKOV3 cells. The 3′UTR of TIMM44 fragment was cloned into the back of Renilla luciferase in the pSicheck2 dual fluorescent reporter to indicate the interaction between HuR and TIMM44. Cell count and MTT assay were performed to assay the proliferation ability of A2780 and SKOV3 cells. High-level HuR expression in 56 ovarian cancer patients recruited in Zibo Central Hospital was positively correlated with metastasis status and poor prognosis revealed by Kaplan–Meier analysis. Both HuR and TIMM44 can promote the proliferation of SKOV3 and A2780 cells. A high correlation of HuR and TIMM44 expression was testified in the TCGA data. Luciferase reporter assay confirmed that HuR could bind to TIMM44 to maintain the mRNA stability. TIMM44 siRNA administration inhibited the proliferation of SKOV3 cells, which could not be rescued. All of these indicate that the main function of HuR on ovarian cancer proliferation is mediated by TIMM44 through mRNA stability regulation, and HuR/TIMM44 complex can be used as a target to inhibit the proliferation of ovarian cancer cells.



中文翻译:

HuR通过调节TIMM44 mRNA稳定性来促进卵巢癌细胞的增殖。

人类抗原R(HuR)在稳定许多肿瘤相关基因的mRNA方面可能起重要作用。很少进行研究以研究HuR介导的促进卵巢癌进展的相关机制。检索癌症基因组图谱(TCGA)数据集以计算HuR与线粒体内膜44(TIMM44)表达。将HuR表达质粒,TIMM44表达质粒,siRNA HuR和TIMM44 siRNA进一步转染到A2780和SKOV3细胞中。将TIMM44片段的3'UTR克隆到pSicheck2双荧光报告基因的海肾荧光素酶的背面,表明HuR和TIMM44之间的相互作用。进行细胞计数和MTT测定以测定A2780和SKOV3细胞的增殖能力。Kaplan–Meier分析显示,在淄博市中心医院招募的56例卵巢癌患者中高水平的HuR表达与转移状态和不良预后呈正相关。HuR和TIMM44均可促进SKOV3和A2780细胞的增殖。HuRTIMM44的高度相关TCGA数据中证实了该表达。荧光素酶报告基因测定证实,HuR可以与TIMM44结合以维持mRNA的稳定性。施用TIMM44 siRNA抑制了SKOV3细胞的增殖,这无法挽救。所有这些表明,HuR对卵巢癌增殖的主要功能是通过TIMM44通过mRNA稳定性调节来介导的,并且HuR / TIMM44复合物可以用作抑制卵巢癌细胞增殖的靶标。

更新日期:2020-09-08
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