MiR-25 and KLF4 relationship has early prognostic significance in the development of cervical cancer

Abstract

Cervical squamous cell carcinoma (SCC) is one of the common cancer types among women. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the formation and development of many cancer types by regulating expression of their targets. While many studies have investigated the relationship between miRNAs and cervical cancer, no robust miRNA biomarkers have been defined yet for diagnosis of cervical lesions. In this study, we performed a statistical meta-analysis to identify miRNAs and a class compassion analysis to evaluate mRNAs with the power to discriminate between normal, intraepithelial lesions and invasive cancer samples. Differentially expressed (DE) mRNAs were compared with the targets of meta-miRNAs. After bioinfomatics analysis and qRT-PCR validations with cytology samples and FFPE tissues, we defined miR-25 and its target KLF4 (Kruppel-like factor 4) as candidate biomarkers for in vitro studies. Our results showed that miR-25 expression was significantly higher in precancerous lesions and invasive carcinoma while presenting consistent expression patterns in both cytological and FFPE tissue samples. In line with this, its direct target KLF4 expression decreased in precancerous lesions in cytological samples and also in the invasive cancer group in FFPE tissues. Furthermore, in vitro studies showed that mir-25 inhibition decreased proliferation and motility of HeLa cells and promoted an increase in the protein level of KLF4. We conclude that inhibition of miR-25 may upregulate KLF4 expression and regulate cell proliferation and motility in cervical cancer.