Mechanism of miR-135a-5p influencing KRT8 expression and epithelial-mesenchymal transition in clear cell renal carcinoma via targeted regulation of TFAP2A

Abstract

Clear cell renal carcinoma (ccRCC) is the most prevalent pathological subtype of renal cell carcinoma. Early symptoms are often insidious, and advanced-stage patients have low sensitivity to radiotherapy and chemotherapy, resulting in poor prognosis. Epithelial-mesenchymal transition (EMT) is the core driver of its invasion and metastasis. Aberrant expression of microRNAs (miRNAs), transcription factors, and keratin is involved in the malignant progression of ccRCC. Among these, miR-135a-5p plays a regulatory role in various tumors, but its systemic regulatory relationship with transcription factor TFAP2A, keratin KRT8, and EMT in ccRCC remains unclear. This article reviews the basic biological characteristics, expression patterns, and biological functions of miR-135a-5p, TFAP2A, and KRT8 in ccRCC, based on recent research progress. The regulatory network of these three genes is analyzed: miR-135a-5p is lowly expressed in ccRCC and exhibits a tumor suppressor effect by inhibiting TFAP2A expression through targeting the 3'-UTR; TFAP2A, as a tumor suppressor gene, is lowly expressed in ccRCC and can target and regulate the expression of KRT8 and EMT-related genes; abnormal KRT8 expression is correlated with the malignancy of ccRCC and affects cell invasion and metastasis by regulating EMT. These three genes form the miR-135a-5p/TFAP2A/KRT8 regulatory axis, jointly participating in the regulation of ccRCC cell proliferation, apoptosis, invasion, metastasis, and prognosis. This article also points out current research limitations and looks forward to future research directions, providing theoretical reference for the molecular mechanism research, early diagnosis, and novel targeted therapies of ccRCC.