Research On The Function Of MiR-125a In Cervical Cancer Growth And Metastasis

Cervical cancer (CC) is a commonly diagnosed gynecological cancer, and the third most common cancer and the fourth leading cause of cancer-related death among women worldwide. More than 80% of these cases are estimated to occur in developing countries. Radiotherapy, chemotherapy, and surgery are standard treatments for CC, but the 5-year survival rate for advanced patients remains very low. Metastasis to the lymph node and distant organs is a major cause of treatment failure. Thus, elucidation of the molecular mechanisms underlying CC tumorigenesis and progression is critical for individualized treatments of CC. It is widely accepted that CC development is related to human papillomavirus (HPV) infection. However, HPV is necessary but not sufficient to cause cervical carcinoma. Thus, other factors must contribute to CC development, including abnormal expression of multiple genes. However, our understanding of the genetic alterations underlying the development of CC remains limited.MicroRNAs (miRNAs) are endogenous non-coding short RNAs that inhibit gene expression by binding to target mRNAs at their 3’-untranslated region (UTR). MiRNAs-mediated regulation of post-transcriptional gene expression has been recently identified in the development and metastasis of many cancer types including CC. Differential expression of miRNAs has been found in cancer and adjacent tissues, suggesting their potential applications as biomarkers and therapeutic targets. Previous studies have indicated that miR-125a is a novel anti-oncogene with low expression in several cancers. However, the association between miR-125a and CC remains unclear.In this study, we found lower expression of miR-125a in CC tissues than in matched non-cancerous tissues. Furthermore, miR-125a inhibits CC cell proliferation and invasion, while suppresses their cell cycle. MiR-125a overexpression reduces cervical tumor growth and metastasis in vivo. Moreover, miR-125a regulates these events by directly binding STAT3 3’-UTR and inhibiting its expression and downstream genes.Thus, overexpression of miR-125a may be a useful strategy for the treatment of CC patients with hyperactivation of STAT3.