Objective To analyze the role and mechanism of Krueppel-like factor 12 (KLF12) gene expression in cervical cancer (CC) caused by human papilloma virus (HPV) integration.

Methods A total of 98 patients undergoing gynecological surgery were selected, including 50 cases of CC, 25 cases of HPV(+) normal cervical epithelium, and 23 cases of cervical intraepithelial neoplasia (CIN). The genomic DNA of samples in each group was obtained, and high-throughput virus integration detection and mass spectrometry were performed to identify integration sites and differential proteins. Gene expression profiling interaction analysis was used to analyze HPV KLF12 expression in CC tissues and non-CC tissues, and the association of KLF12 expression with overall survival in CC patients was analyzed. The expression of KLF12 in CC tissues was detected by immunohistochemistry, and the relationship between KLF12 expression and clinicopathological features was evaluated. In experiments in vitro, HeLa cells were divided into KLF12 knockdown (si-KLF12) group and corresponding control (si-NC) group; cell viability was assessed by CCK-8 and EdU incorporation assays, respectively, and cell migration and invasion abilities were detected by Transwell assay.

Results In all cervical samples, the overall prevalence of HPV integration was 72.1% (137/190). Compared with the normal group, the number of HPV integration in the CIN group and tumor group decreased (P < 0.05), and the number of HPV integration in the tumor group was higher than that in the CIN group (P < 0.05). In terms of gene structure, HPV integration frequently occurred in the intron of CCAT1 and the intergenic region between KLF5/KLF12. The GEPIA26 study showed that the survival of CC patients with elevated KLF12 was reduced (P < 0.05). The immunohistochemical staining results showed that compared with normal cervical tissue, KLF12 expression was significantly upregulated in cervical cancer tissue (P < 0.01).The results of in vitro cell experiments showed that KLF12 knockdown reduced the proliferation, migration, and invasion ability of HeLa cells.

Conclusions KLF12 may serve as a suggestive candidate risk locus for cervical HPV infection and persistence. KLF12 is upregulated in CC cell lines and tissues, and its high expression promotes the proliferation and invasion of cervical cancer cells in vitro.