TMEM132A to promote cervical cancer progression via HOMER3-mediated activation of FAK/PI3K/AKT signaling pathway.

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Background: TMEM132A exhibits aberrant expression in various types of solid tumors. However, its biological roles and underlying molecular mechanisms in cervical cancer (CC) are still mainly unknown. Methods: To investigate the expression pattern of TMEM132A in CC, transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were integrated and assessed. The differential expression of TMEM132A was verified in CC cell lines (HcerEpic, C-33A, CaSki, and SiHa) as well as in three pairs of matched tumor and neighboring healthy tissue samples via western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). Functional assays, such as CCK-8 for cell proliferation, Transwell assays for invasion, and flow cytometry for cell cycle analysis, were systematically performed to evaluate the oncogenic roles of TMEM132A. Gene set enrichment analysis (GSEA) and co-expression network analysis were employed to identify potential downstream signaling pathways. Furthermore, rescue experiments involving TMEM132A overexpression or knockdown combined with HOMER3 interference were conducted to elucidate the mechanistic interactions. Results: MEM132A was significantly overexpressed in CC tissues and cell lines, and its expression was strictly linked to aggressive tumor progression. Functional studies revealed that TMEM132A overexpression noticeably triggered cell aggressiveness and progression via the S phase of the cell cycle, while knockdown of TMEM132A reversed these effects. Mechanistically, TMEM132A facilitated CC progression by stimulating the FAK/PI3K/AKT pathway, an effect that was dependent on its positive regulation of the downstream effector HOMER3. Importantly, rescue experiments demonstrated that silencing HOMER3 effectively attenuated the oncogenic effects induced by TMEM132A overexpression. Conclusions: This study is the first to demonstrate that TMEM132A promotes CC progression through HOMER3-dependent stimulation of the FAK/PI3K/AKT axis. These outcomes underline TMEM132A as a potential innovative diagnostic biomarker and a promising therapeutic target in CC.