Biological Function of MicroRNA193a-3p in Health and Disease

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs that act mainly as negative regulators of gene expression. Several studies demonstrated that miRNAs take part in numerous biological processes, such as proliferation, apoptosis, and migration. The dysregulation of miRNAs has been frequently observed in different types of disease, including cancer. Here, we provide a comprehensive review on the human miR-193a-3p by considering its role in both physiological and pathological contexts. Different mechanisms involved in regulating miR-193a-3p expression have been reported, including epigenetic modifications and transcription factors. In physiological contexts, miR-193a-3p seemed able to limit proliferation and cell cycle progression in normal cells. Remarkably, several publications demonstrated that miR-193a-3p acted as a tumor suppressor miRNA in cancer by targeting different genes involved in proliferation, apoptosis, migration, invasion, and metastasis. Furthermore, the downregulation of miR-193a-3p has been observed in many primary tumors and altered levels of circulating miR-193a-3p have been identified in serum or plasma of cancer patients and subjects affected by Parkinson's disease or by schizophrenia. In a clinical perspective, further studies are needed to explore the antitumor effects of the miR-193a-3p mimics delivery and the relevance of this miRNA detection as a possible diagnostic and prognostic biomarker.

Figure 1

Genomic location of miR-193a coding sequence, stem-loop hairpin structure of pre-miR-193a and miR-193a-3p/miR-193a-5p sequences. (a) The analysis of the genomic region coding miR-193a referred to Genome Browser (https://genome-euro.ucsc.edu/). MIR193a coding sequence is located on human chromosome 17q11.2 characterized by a typical CpG island (in green). The layered H3K27Ac, H3K4Me1, and H3K4Me3 show the levels of histone marks across the genome in 7 cell lines (data obtain from ENCODE on the basis of ChiP-seq assay). By default, this track displays data from a number of cell lines in the same vertical space and each of the cell line is associated with a particular color. The regulatory element (in orange) is described as transcription factor binding sites by ORegAnno (open regulatory annotation). (b) The MIR193a gene is transcribed into a precursor (pre-miR-193a) with 88 nucleotides that is processed during miRNA biogenesis to yield mature miR-193a-5p (in red) and mature miR-193a-3p (in green) with 22 nucleotides in length.

Figure 2

Expression profile of miR-193a in normal tissues. The expression level of miR-193a is reported for 51 tissues and 2 cell lines (EBV-transformed lymphocytes and transformed fibroblasts) and is referred to GTEx project collected in Genome Browser. Expression values are shown in RPKM (reads per kilobase of transcript per million mapped reads). The height of each bar represents the median expression level across all samples for a tissue, and points are outliers if they are above or below 1.5 times the interquartile range. Each color represents a specific tissue, conformed to GTEX consortium publication convention.

Figure 3

Proposed model for the role of miR-193a-3p in the regulation of the chemoresistance in different cancer cell lines. (a) Involvement of high miR-193a-3p expression level in chemoresistance in HCC cells, BCa cells, and esophageal cancer cells. (b) Low levels of miR-193a-3p are involved in resistance to oxaliplatin in colon cancer cells. Altered expression of miR-193a-3p will adversely affect immediate targets indicated inside black boxes. In turn, these targets will affect several downstream pathways with green arrows and red lines representing functional activation and repression, respectively.