RSRC1 is a candidate progression-associated biomarker in cervical cancer linked to p53/CDK2-associated cell-cycle signaling.

چکیده اصلی

Cervical cancer (CC) remains a leading cause of cancer-related death among women, and the outlook for patients with advanced, recurrent or persistent disease is poor. Molecular markers that track disease progression and expose pharmacologically tractable vulnerabilities are therefore needed. GSE63514 and GSE138080 were used for exploratory candidate generation and cohort-specific disease-stage and discrimination analyses; random forest analysis was restricted to candidate prioritization. Prognostic relevance was assessed in TCGA-CESC (n = 304). Two independent siRNAs silenced RSRC1 in SiHa and CaSki cells, followed by viability, DNA synthesis, migration, cell-cycle and p53/CDK2 analyses. CDK2 overexpression, treatment with the p53 inhibitor pifithrin-α and a stable shRNA xenograft model evaluated pathway involvement and in vivo effects. RSRC1 expression increased across cervical disease stages. In GSE138080, RSRC1 discriminated cervical squamous cell carcinoma from non-carcinoma samples (area under the curve = 0.972, 95% confidence interval 0.925-1.000). High RSRC1 expression was associated with shorter overall survival (hazard ratio = 2.45, 95% confidence interval 1.55-3.87; P < 0.001) and remained independently associated after multivariable adjustment. In both cell lines, either siRNA reduced viability, DNA synthesis and migration, induced G2/M accumulation, increased p53 and decreased CDK2. CDK2 overexpression or pifithrin-α partially reversed these phenotypes. Stable RSRC1 depletion slowed xenograft growth, reduced Ki-67 and CDK2, and increased p53. RSRC1 is a candidate progression-associated biomarker that supports CC cell proliferation and migration. The findings support partial involvement of p53/CDK2-associated signaling, while independent clinical validation and direct characterization of RSRC1-regulated splicing remain necessary.

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