MiR‐23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells

Abstract

Copy number variation (CNV) and abnormal expression of microRNAs (miRNAs) always lead to deregulation of genes in cancer, including gastric cancer (GC). However, little is known about how CNVs affect the expression of miRNAs. By integrating CNV and miRNA profiles in the same samples, we identified eight miRNAs (miR-1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2) that were located in the amplified regions and were upregulated in GC. In particular, amplification of miR-23a-27a-24-2 cluster and miR-181c-181d cluster frequently occurred at 19p13.13 and were confirmed by genomic real-time PCR in another 25 paired GC samples. Moreover, in situ hybridization (ISH) experiments represented that mature miR-23a was increased in GCs (75.5%, 40/53) compared with matched normal tissues (28.6%, 14/49, P = 0.001). Knocking down of miR-23a expression inhibited BGC823 cell growth in vitro and in vivo. In addition, the potential target genes of miR-23a were investigated by integration of mRNA profile and miRNA TargetScan predictions, we found that upregulation of miR-23a and downregulation of metallothionein 2A (MT2A) were detected simultaneously in 70% (7/10) of the miRNA and mRNA profiles. Furthermore, an inverse correlation between miR-23a and MT2A expression was detected in GCs and normal tissues. Through combining luciferase assay, we confirmed that MT2A is a potential target of miR-23a. In conclusion, these results suggest that integration of CNV-miRNA-mRNA profiling is a powerful tool for identifying molecular signatures, and that miR-23a might play a role in regulating MT2A expression in GC.

miR-24-3p Regulates Progression of Gastric Mucosal Lesions and Suppresses Proliferation and Invasiveness of N87 Via Peroxiredoxin 6

“…Many miRNAs are closely associated with GC, but knowledge of their abnormal expression and potential role in GC is inadequate. Eight miRNAs (miR1274a, miR196b, miR4298, miR181c, miR23a, miR27a, and miR-24-2) were reported to be highly expressed in GC tissue [9]. Combining this result with bioinformatics analysis on Prdx-6, which has been intensively investigated in our previous study [8], we selected miR-24-3p for further study.…”

“…In addition, bioinformatics prediction indicated that there are five miRNAs that might regulate Prdx-6 expression level (hsa-miR-24, hsa-miR-186, hsa-miR-149, hsa-miR-124, and hsa-miR-506). Based on the integrated analysis of copy number variations (CNVs), genomic alterations, miRNA expression profiling, microRNA 24 drew our attention and it has two gene subtypes—miR-24-3p, miR-24-5p [9]. After preliminary experiments, miR-24-3p was found to be highly expressed in GC.…”

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

“…143 By integrating CNV and miRNA profiles in the same samples, the authors identified eight miRNAs (miR--1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2) that were located in the amplified regions and were upregulated in GC. The amplification of miRNAs were confirmed by real-time PCR and in situ hybridization assays.…”

Involvement of miR-20a in Promoting Gastric Cancer Progression by Targeting Early Growth Response 2 (EGR2)

“…miRNAs functioned as oncogenes or tumor suppressors by regulating different target gene expression in different cancers. miR-9, miR-22, and miR-146a had all been shown to act as tumor suppressors [9–11], whereas miR-19, miR-23a, and miR-301a had been shown to function as oncogenes [12–14]. These studies suggested that dysregulation of miRNAs might be involved in carcinogenesis and cancer progression.…”