Overexpression of FEN1 promotes cervical cancer progression via upregulating PCNA expression

Cervical cancer stands as a prevalent gynecological malignancy. The purpose of this study is to discover new therapeutic targets for cervical cancer. To identify key genes associated with cancer, we analyzed transcriptome expression data of various cancers from TCGA. CCK-8 assays, colony formation assays, wound-healing assays, transwell assays and apoptosis assays were used to investigate their functions. qRT-PCR and Western Blot were utilized to verify their expression. RESULTS: A total of 358 common key genes were identified in six common cancers. Immunohistochemical experiments revealed that FEN1 was significantly overexpressed in cervical cancer. Compared to the control group, knocking down FEN1 markedly inhibited the proliferation, colony formation, migration and invasion capabilities of SiHa and HeLa, while simultaneously promoting apoptosis. In both SiHa and HeLa cells, knockdown of FEN1 significantly reduced the expression of PCNA. PCNA knockdown exerted nearly identical inhibitory effects on the malignant phenotypes of these two cell lines as FEN1 depletion. Subsequent rescue experiments verified that restoring PCNA expression could partially reverse the suppressive effects of FEN1 knockdown on the malignant behaviors of cervical cancer cells. Moreover, FEN1 silencing in both SiHa and HeLa cells also led to a significant decrease in the expression levels of BCL-2 , RB1 and PIK3CA , while increasing the expression of Caspase-9 . CONCLUSION: FEN1 exhibits a significant overexpression in cervical cancer and has the capacity to modify the biological behavior of cancer cells, potentially via regulating the expression of PCNA . Inhibiting FEN1 expression may slow down the progression of cervical cancer.