HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability.

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.