ITGA5 promotes cervical cancer progression by regulating IMP3 recruitment of HK2 mRNA.

Abstract

Cervical cancer is a prevalent gynecologic malignancy characterized by high rates of invasion and metastasis. Integrin alpha 5 (ITGA5), a member of the integrin family, has been implicated in tumor progression; however, its regulatory role in cervical cancer remains poorly defined. Bioinformatic analyses revealed elevated ITGA5 expression in cervical cancer, which was further validated in patient tissues by immunohistochemistry (IHC). ITGA5 was either silenced or overexpressed in cervical cancer cell lines, and its effects on proliferation, invasion, and migration were assessed using CCK-8, Transwell, and wound healing assays. The in vivo effects of ITGA5 knockdown were evaluated through subcutaneous tumor xenografts in nude mice. Mass spectrometry identified insulin-like growth factor II mRNA binding protein 3 (IMP3) as a potential ITGA5-interacting protein. Their interaction was confirmed using co-immunoprecipitation (CO-IP), western blotting, and RNA immunoprecipitation (RIP). ITGA5 was found to be significantly upregulated in cervical cancer and negatively correlated with patient survival. Functionally, ITGA5 promoted proliferation, invasion, and migration of cervical cancer cells in vitro and enhanced tumor growth in vivo. Mechanistically, ITGA5 interacted with IMP3, regulating the recruitment of hexokinase 2 (HK2) mRNA by IMP3. Overexpression of HK2 rescued the inhibitory effects of ITGA5 knockdown on cervical cancer progression. This study presents new findings on the pathogenesis of cervical cancer and identifies a possible therapeutic target.