HIF-1α activates hypoxia-induced MXRA5 expression in the progression of ovarian cancer

Abstract

Background: The hypoxic microenvironment of tumor cells is closely related to the progression of ovarian cancer. This study aims to explore the role of matrix-remodeling associated 5 (MXRA5) in regulating cellular hypoxia in ovarian cancer. Methods: The MXRA5 expression and its clinical significance in ovarian cancer were evaluated using GEPIA2, Kaplan-Meier plotter databases, and immunohistochemistry assay. Ovarian cancer cells were treated with normoxia and hypoxia conditions. The siRNAs were used to knock down the MXRA5 expression in hypoxic cells. The cellular capacities were detected by CCK-8 assay, EdU assay, Transwell invasion assay, and TUNEL assay, respectively. Results: The MXRA5 level was increased in ovarian cancer and associated with the PFS and survival of ovarian cancer patients. The proliferation and invasion abilities of ovarian cancer cells were promoted, while apoptosis capacities were inhibited in hypoxic cells. After the knockdown of MXRA5 in hypoxic cells, the proliferation and invasion abilities of the cells were reduced, and the apoptosis capacities were enhanced. Moreover, mechanistically, HIF-1α is a key transcription factor in response to hypoxia that binds to the MXRA5 promoter. Conclusion: MXRA5 expression was induced by hypoxia and had prognostic performance in ovarian cancer. MXRA5 is one of the potential targets of tumor hypoxia regulation. Knockdown of MXRA5 can inhibit proliferation and invasion in ovarian cancer cells caused by HIF-1α, revealing that MXRA5 is one potential targets for tumor hypoxia regulation in ovarian cancer.