Epigenetic regulation of miR‐34b and miR‐129 expression in gastric cancer

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in diverse biological and pathological processes by targeting the expression of specific genes. Here, we identified 38 methylation-associated miRNAs, the expression of which could be epigenetically restored by cotreatment with 5-aza-2 0 -deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR-34b, miR-127-3p, miR-129-3p and miR-409 because CpG islands are predicted adjacent to them. The methylation-silenced expression of these miRNAs could be reactivated in gastric cancer cells by treatment with demethylating drugs in a time-dependent manner. Analysis of the methylation status of these miRNAs showed that the upstream CpG-rich regions of mir-34b and mir-129-2 are frequently methylated in gastric cancer tissues compared to adjacent normal tissues, and their methylation status correlated inversely with their expression patterns. The expression of miR-34b and miR-129-3p was downregulated by DNA hypermethylation in primary gastric cancers, and the low expression was associated with poor clinicopathological features. In summary, our study shows that tumor-specific methylation silences miR-34b and miR-129 in gastric cancer cells.

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

“…Recently, it was reported that miR-409 may be subjected to epigenetic modulation in GC, which in turn may be responsible for miR-409-3p downregulation in GC. 33 Taken together, these results suggest that reduced miR-409-3p is a frequent event in human GC and that patients with downregulated miR-409-3p are prone to lymph node metastasis. The capability of cell migration and invasion is considered to be one of the important determinants in the process of cancer metastasis.…”

Aberrant hypermethylation ofmiR-9genes in gastric cancer

“…These results indicate that dysregulation of hypermethylation concurrently regulates the three pri-miR-9 paralogous human AGS gastric cancer cells following the treatment of DNA demethylation agents and identified several methylation-associated miRNAs, including miR-9. 9 We now demonstrated that the expression levels of mature miR-9 were modulated through DNA demethylation treatment at various time periods (0-4 days after treatment) in AGS cells (Fig. 1A).…”

“…Recent studies have indicated that several miRNAs, including miR-34b/c, miR-129, miR-137, miR-181C, miR-199a, miR-212, miR-512 and miR-516, were dysregulated and showed aberrant methylation patterns in gastric cancer cells. 6,9,[14][15][16][17][18][19][20][21] The three pri-miR-9 transcripts are all located within non-protein coding transcripts (Fig. 2A).…”

“…[2][3][4] Previous studies have shown that many miRNAs are aberrantly overexpressed or downregulated during gastric cancer progression, including miR- 16, miR-21, miR-101, miR-126, miR-129, miR-181c, miR-196b and -200. [5][6][7][8][9][10][11][12] These miRNAs could play oncogenic or tumor-suppressive functions in the regulation of cell growth, apoptosis and cell migration by repressing their target genes.…”

MiR-129-5p is down-regulated and involved in migration and invasion of gastric cancer cells by targeting interleukin-8

“…Recently, emerging evidence suggested that miRNAs play significant roles in the initiation, progression, and survival prediction of GC by regulating cell proliferation, invasion, and migration [5,6]. MiR-129-5p, one of the mature forms of miR-129-1 and miR-129-2, has been reported to be involved in various neoplastic processes, including GC [7][8][9]. It has been demonstrated that miR-129-5p serves as an important tumor suppressor, and overexpression of miR-129-5p could significantly decrease the cell proliferation activity of multiple tumor cell lines, such as endometrial tumor cells, lung adenocarcinoma cell lines, bladder cancer cells, and GC cells [7,[10][11][12].…”