PGRMC1 Promotes the Development of Cervical Intraepithelial Neoplasia in HPV-Positive Patients.

Background/Objectives: Persistent human papillomavirus (HPV) infection is the leading cause of cervical intraepithelial neoplasia (CIN), a known precursor to cervical squamous carcinoma. While progesterone receptor membrane component 1 (PGRMC1) has been implicated in various cancers, its specific role in cervical carcinogenesis has remained uncertain. This study aimed to elucidate the function of PGRMC1 in the progression of CIN. Methods: Bioinformatics techniques were employed to assess the expression levels of PGRMC1 in cervical cancer tissues and to investigate its correlation with patient prognosis. To explore the functional role of PGRMC1, we manipulated its expression in the cervical cancer cell line HeLa using siRNA. Subsequently, we evaluated cell migration via the scratch assay, and invasion through the Transwell assay. We employed mass spectrometry to identify proteins interacting with PGRMC1 and confirmed these interactions using co-immunoprecipitation (co-IP). Further co-IP experiments were conducted to pinpoint the specific binding sites of these protein interactions, and immunofluorescence staining was utilized to observe the spatial distribution of interacting proteins within the cells. The phosphorylation status of VIM was further confirmed by WB. At the clinical level, we collected cervical biopsy specimens from HPV-positive patients and verified the expression patterns of PGRMC1 and VIM using immunohistochemical staining in cervical squamous cell carcinoma (CSCC) tissues. Results: We discovered a correlation between progressively increasing PGRMC1 expression and the severity of CIN as well as a poor prognosis. Knockdown of PGRMC1 resulted in the inhibition of migration and invasion capabilities in cervical cancer cells. Furthermore, PGRMC1 was found to physically interact and colocalize with Vimentin (VIM). Notably, PGRMC1 knockdown specifically increased phosphorylation at the Ser-39 residue of VIM. Conclusions: Our findings suggest that PGRMC1 facilitates CIN progression by binding to VIM and suppressing Ser-39 phosphorylation, thereby promoting the migration and invasion of cervical carcinoma cells. This study enhances our understanding of PGRMC1's role in CIN progression and lays an experimental foundation for targeted therapeutic approaches to cervical squamous carcinoma.