Abstract
BackgroundLong noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined.MethodsQuantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis.ResultsMEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a.ConclusionsThese findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.
Highlights
The ENCODE project showed that ~80 % of the human genome is transcribed to RNA, with only ~2 % being responsible for protein coding
These findings suggest that Long noncoding RNAs (lncRNAs) Maternally expressed gene 3 (MEG3), a competing endogenous RNA (ceRNA) of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies
We showed that a lncRNA, maternally expressed gene 3 (MEG3) is decreased in gastric cancer (GC) patients and cell lines, and its expression was associated with metastatic GC
Summary
The ENCODE (encyclopedia of DNA elements) project showed that ~80 % of the human genome is transcribed to RNA, with only ~2 % being responsible for protein coding. According to their size, non-coding RNAs (ncRNAs) are classified into small ncRNAs and long ncRNAs (lncRNAs). Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined
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