Comprehensive analysis of VDAC1 in gynecological tumors and structure-based virtual screening of its natural inhibitors.

Abstract

The voltage-dependent anion channel 1 (VDAC1) protein is an important regulator of mitochondrial function. The aim of this study was to investigate the role of VDAC1 in gynecological malignancies, and to screen the natural compounds targeting VDAC1, as the candidate anti-cancer drugs. The expression levels of VDAC1 mRNA and protein were analyzed using the GEPIA and UALCAN databases. The TISIDB database was used to analyze the correlation between VDAC1 expression and tumor stage, histological grade and immunomodulators. The pan-cancer prognostic value of VDAC1 was evaluated using the GEPIA2 database. Genetic Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R software clusterProfiler package. The relationship between VDAC1 expression and immune cell infiltration in gynecological tumors was analyzed using the TIMER database. Potential compounds targeting VDAC1 were screened by virtual screening and molecular docking. After VDAC1 was silenced or aloe-emodin treatment, the expressions of VDAC1, Bcl-2 and Bax in cancer cells were detected by RT-qPCR and Western blot, and cancer cell proliferation was detected by CCK-8 assay, and apoptosis was evaluated by flow cytometry, and migration of the cancer cells were examined with Transwell assay. It was revealed that, VDAC1 was highly expressed in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), uterine corpus endometrial carcinoma (UCEC) and ovarian cancer (OV). High expression of VDAC1 was associated with higher tumor stage and poor prognosis of CESC, as well as high histological grade and immune subtypes of UCEC. Knocking down VDAC1 repressed the proliferation and migration of CESC, UCEC and OV cells, and promoted the apoptosis of tumor cells. Aloe-emodin showed strong binding affinity with VDAC1 protein, and it showed tumor-suppressive properties against CESC, UCEC and OV cells. In conclusion, VDAC1 may be a potential diagnostic biomarker and a new target for gynecological malignancies, and aloe-emodin is a candidate anti-cancer drug targeting VDAC1.