miR-33b in human cancer: Mechanistic and clinical perspectives

The microRNAs (miRNAs), an extensive class of small noncoding RNAs (similar to 22 nucleotides), have been shown to have critical functions in various biological processes during development. miR-33b (or hsa-miR-33b) is down-regulated in cancer of multiple systems. Notably, at least 27 protein-coding genes can be targeted by miR-33b. miR-33b regulates the cell cycle, cell proliferation, various metabolism pathways, epithelial-mesenchymal transition (EMT), cancer cell invasion and migration, etc. In prostate cancer, Cullin 4B (CUL4B) can be recruited to the promoter to inhibit the expression of miR-33b. In gastric cancer, the hypermethylation of the CpG island regulated the expression of miR-33b. Besides, miR-33b could be negatively regulated by 7 competing-endogenous RNAs (ceRNAs), which are all long non-coding RNAs (lncRNAs). There are at least 4 signaling pathways, including NF-kappa B, MAP8, Notch1, and Wnt/beta-catenin signaling pathways, which could be regulated partially by miR-33b. Additionally, low expression of miR-33b was associated with clinicopathology and prog-nosis in cancer patients. In addition, the aberrant expression of miR-33b was connected with the resistance of cancer cells to 5 anticancer drugs (cisplatin, docetaxel, bortezomib, paclitaxel, and daunorubicin). Importantly, our work systematically summarizes the aberrant expression of miR-33b in various neoplastic diseases and the effect of its downregulation on the biological behavior of cancer cells. Furthermore, this review focuses on recent advances in understanding the molecular regulation mechanisms of miR-33b. Moreso, the relationship between the miR-33b expression levels and the clinicopathological data and prognosis of tumor patients was summarized for the first time. Overall, we suggest that the current studies of miR-33b are insufficient but provide potential hints and direction for future miR-33b-related research.

Automated summary

miR-33b is a critical microRNA that is down-regulated in cancer cells and affects the biological behavior of cancer cells by regulating multiple signaling pathways. The abnormal expression of miR-33b is associated with the clinicopathological data and prognosis of tumor patients. This study systematically summarizes the regulatory mechanisms of miR-33b and provides potential hints and direction for future miR-33b-related research.