ABSTRACT
Members of ONECUT transcription factor play an essential role in several developmental processes, however, the atypical expression of ONECUT proteins lead to numerous diseases, including cancer. ONECUT family proteins promote cell proliferation, progression, invasion, metastasis, angiogenesis, and stemness. This family of proteins interacts with other proteins such as KLF4, TGF-ß, VEGFA, PRC2, SMAD3 and alters their expression involved in the regulation of various signaling pathways including Jak/Stat3, Akt/Erk, TGF-ß, Smad2/3, and HIF-1α. Furthermore, ONECUT proteins are proposed as predictive biomarkers for pancreatic and gastric cancers. The present review summarizes the involvement of ONECUT family proteins in the development and progression of various human cancers and other diseases.
Subject(s)
Kruppel-Like Factor 4 , Neoplasms , Transcription Factors , Humans , Neoplasms/metabolism , Neoplasms/genetics , Neoplasms/pathology , Transcription Factors/metabolism , Transcription Factors/genetics , Signal Transduction , Animals , Cell Proliferation/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. Due to the absence of obvious therapeutic targets, microRNAs (miRNAs) provide possible hope to treat TNBC. Withaferin A (WA), a steroidal lactone, possesses potential anticancer activity with lesser side effects. The present study identifies hub genes (CDKN3, TRAF6, CCND1, JAK1, MET, AXIN2, JAG1, VEGFA, BRCA1, E2F3, WNT1, CDK6, KRAS, MYB, MYCN, TGFßR2, NOTCH1, SIRT1, MYCN, NOTCH2, WNT3A) from the list of predicted targets of the differentially expressed miRNAs (DEMs) in WA-treated MDA-MB-231 cells using in silico protein-protein interaction network analysis. CCND1, CDK6, and TRAF6 hub genes were predicted as targets of miR-34a-5p and miR-146a-5p, respectively. The study found the lower expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells, and further, it was observed that WA treatment effectively restored the lost expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells. An anti-correlation expression pattern was found among the miR-34a-5p and miR-146a-5p and the respective target hub genes in WA-treated TNBC cells. In conclusion, WA might exert anti-cancer effect in TNBC cells by inducing miR-34a-5p and miR-146a-5p expressions and decreasing CCND1, CDK6, and TARF6 target hub genes in TNBC cells.
