LncRNA FAM83H-AS1 contributes to the radioresistance, proliferation, and metastasis in ovarian cancer through stabilizing HuR protein

Abstract

Ovarian cancer (OC) is a major cause of cancer-related deaths in women all over the world. The easy metastasis of OC and the problem of radioresistance are serious issues remaining to be overcome. Thus, research on molecular mechanisms underlying is in urgent demand. Long non-coding RNAs (lncRNAs) are a class of RNAs without protein coding potential, which has been reported to participate in the regulation on multiple biological process in cancers, including cell radiosensitivity and metastasis. Present study aimed to explore the role of lncRNA FAM83-AS1 in radioresistance and metastasis of ovarian cancer. First of all, the obvious upregulation of FAM83H-AS1 was identified by qRT-PCR in OC tissues, especially in metastatic tissues, as well as in OC cell lines. Importantly, we confirmed the correlation of FAM83H-AS1 levels with both ovarian cancer cells and normal ovarian cells. And Kaplan-Meier analysis indicated FAM83H-AS1 as a potential target of poor prognosis of OC. Through loss-of-function assays, we validated the inductive effect of FAM83H-AS1 in OC cell metastasis and radioresistance. Through mechanism research on FAM83H-AS1, we confirmed its interaction with HuR using pull-down assay and RNA immunoprecipitation (RIP), and verified the stabilization of HuR protein by FAM83-AS1 through western blot with the addition of CHX. Finally, rescue assays showed that overexpression of HuR rescued the suppression on radioresistance and metastasis in OC cell caused by the silencing of FAM83H-AS1. In conclusion, present study proved that FAM83H-AS1 contributes to the radioresistance and cell metastasis in ovarian cancer through stabilizing HuR protein.