Functions and underlying mechanisms of miR-650 in human cancers

Abstract

MicroRNAs (miRNAs) are one type of noncoding RNAs that interfere with mRNA translation to downregulate gene expression, which results in posttranscriptional gene silencing. Over the past two decades, miRNAs have been widely reported to impact the progression of malignant tumours by interfering with cancer initiation and progression; therefore, miRNAs represent potential new diagnostic and therapeutic tools. miR-650 is a newly identified miR, and increasing studies have demonstrated that miR-650 plays critical roles in cancer progression, such as mediating the Wnt signalling pathway/AXIN1 (axis inhibition protein 1) axis in hepatocellular carcinoma. Nevertheless, associations between the expression patterns and molecular mechanisms of miR-650 in cancer have not been comprehensively described. In this article, we review the existing evidence regarding the mechanisms by which miR-650 expression is altered and their relation to cancer. Moreover, the promising clinical application of miR-650 for diagnosis and treatment is highlighted.

Keywords: Biological roles; Cancer; Expression; MiR-650; Oncogenesis.

Fig. 1

Upstream regulation of miR-650. Multiple factors participate in the upstream regulation of the miR-650 biological process. In the nucleus, transcription of miR-650 is modulated by coupling expression with its homologous gene immunoglobulin lambda and promoted by transcription factors PBX1 and NF-kB. In the cytoplasm, AXIN1 and lncRNAs (DICER-AS1, MEG3, MIR155HG, POU3F3, ZFPM2-AS1, MCTP1-AS1), which account for the major alterations, act as molecular sponges for miR-650 and negatively regulate its biological function, inducing cancer gene deregulation

Fig. 2

Target regulators of miR-650, related signalling pathways and induced biological effects. Genesis, differentiation and metastasis of tumours are essentially related to diverse intracellular signalling pathways, such as Jagged/Notch1, TGFβ/SMAD, Wnt/β-Catenin, and FAT/LATS2, which deliver multiple signals to the cell nucleus in a cascade mode and then trigger a series of biological effects. miR-650 functions as a tumour promoter or suppressor by posttranscriptionally regulating the pivotal factors (oncogenic or anti-oncogenic) within these cascades to affect various biological processes, including cell cycle arrest, proliferation, apoptosis, migration, invasion and EMT. The integrated signalling pathways and key factors directly targeted by miR-650 (white blue) are shown