HIF-1α Activates Hypoxia-Induced MXRA5 Expression in the Progression of Ovarian Cancer.

Abstract

The hypoxic microenvironment of tumor cells is closely related to the progression of ovarian cancer (OV). Hypoxia (HY)-related matrix-remodeling associated 5 (MXRA5) was expressed at elevated levels in many tumors, but research on the impact of MXRA5 in OV remains limited. This study aims to explore the role of MXRA5 in regulating cellular HY in OV. The MXRA5 expression and its clinical significance in OV were evaluated using GEPIA2, Kaplan-Meier plotter databases, and immunohistochemistry assay. OV cells were treated with normoxia and HY conditions. The siRNAs were designed to knock down the MXRA5 expression in hypoxic cells. The cellular capacities were detected by CCK-8 assay, EdU assay, Transwel assay, and TUNEL assay, each method targeting a different aspect of cellular behavior. The MXRA5 level was increased in OV and associated with the progression free survival and overall survival of OV patients. The proliferation and invasion abilities of OV cells were promoted, while apoptosis capacities were inhibited in hypoxic cells. After the knockdown of MXRA5 in hypoxic cells, the proliferative capacities and invasive abilities of the cells were reduced, and the apoptosis capacities were enhanced. Moreover, mechanistically, HIF-1α is a key transcription factor in response to HY that binds to the MXRA5 promoter. MXRA5 expression was induced by HY and had prognostic performance in OV. Knockdown of MXRA5 can inhibit proliferation and invasion in OV cells caused by HIF-1α, revealing that MXRA5 is one potential targets for tumor HY regulation in OV.