MicroRNA-375: potential cancer suppressor and therapeutic drug

Abstract

MiR-375 is a conserved noncoding RNA that is known to be involved in tumor cell proliferation, migration, and drug resistance. Previous studies have shown that miR-375 affects the epithelial-mesenchymal transition (EMT) of human tumor cells via some key transcription factors, such as Yes-associated protein 1 (YAP1), Specificity protein 1 (SP1) and signaling pathways (Wnt signaling pathway, nuclear factor κB (NF-κB) pathway and transforming growth factor β (TGF-β) signaling pathway) and is vital for the development of cancer. Additionally, recent studies have identified microRNA (miRNA) delivery system carriers for improved in vivo transportation of miR-375 to specific sites. Here, we discussed the role of miR-375 in different types of cancers, as well as molecular mechanisms, and analyzed the potential of miR-375 as a molecular biomarker and therapeutic target to improve the efficiency of clinical diagnosis of cancer.

Keywords: Dysregulation; EMT; Tumor-suppressive; miR-375.

Figure 1. The activation of EMT

EMT-related signaling pathways are essential for the occurrence of EMT. EMT allows tumor cells to invade and metastasize and may also allow tumor cells to escape apoptosis.

Figure 2. Schematic diagram of the mechanism of miR-375 in EMT

MiR-375 attenuates EMT by inhibiting vital target genes (such as YAP1, SP1, SNAIL1, HOXB13, YWHAX). EMT can also be enhanced by inhibiting E-cadherin. Additionally, some signaling pathways related to EMT also act as intermediaries between miR-375 and EMT. For example, miR-375 inhibits the expression of RBPJ and Notch2 to inhibit the NOTCH pathway, while miR-375 also inhibits the WNT pathway by reducing the expression of YWHAZ. Also, miR-375 reduces the activity of the TGF-β pathway by inhibiting the expression of SHOS2. Finally, miR-375 inhibits the AKT signaling pathway by inhibiting the level of IGF1R, regulating EMT.