Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1

Abstract

Background: In recent decades, long non-coding RNAs (lncRNAs) have been reported as crucial functional regulators involved in ovarian cancer. In the present study, we explored how lncRNA RHPN1-AS1 influences the progression of epithelial ovarian cancer (EOC) through tumor cell-dependent mechanisms. Results: The expression of RHPN1-AS1 in EOC tissues was higher than that in para-cancerous control tissues. High expression of RHPN1-AS1 was closely associated with poor prognosis in EOC patients. N6-methyladenosine (m6A) improved the stability of RHPN1-AS1 methylation transcript by reducing RNA degradation, which resulted in upregulation of RHPN1-AS1 in EOC. In vitro and in vivo functional experiments showed that RHPN1-AS1 promoted EOC cell proliferation and metastasis. RHPN1-AS1 acted as a ceRNA to sponge miR-596, consequently increasing LETM1 expression and activating the FAK/PI3K/Akt signaling pathway. Conclusion: RHPN1-AS1-miR-596-LETM1 axis plays a crucial role in EOC progression. Our findings may provide promising drug targets for EOC treatment. Methods: We determined the aberrantly expressed lncRNAs in EOC via microarray analysis and validated RHPN1-AS1 expression by qRT-PCR. The RHPN1-AS1-miR-596-LETM1 axis was examined by dual-luciferase reporter assay and RIP assay. The mechanism of RHPN1-AS1 was investigated through gain-and loss-of-function studies both in vivo and in vitro.