Abstract
microRNA-27a (miR-27a) is frequently dysregulated in human carcinoma, including gastric cancer. The B-cell translocation gene 2 (BTG2) has been implicated in gastric carcinogenesis. However, till now, the link between miR-27a and BTG2 in gastric cancer has not been reported. Here, we found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p. And overexpression of miR-27a-3p, but not miR-27a-5p, markedly promoted gastric cancer cell proliferation in vitro as well as tumor growth in vivo. Further experiments revealed that BTG2 was a direct and functional target of miR-27a-3p in gastric cancer and miR-27a-3p inhibition obviously up-regulated the expression of BTG2. In turn, overexpression of BTG2 triggered G1/S cell cycle arrest, induced subsequent apoptosis, and inhibited C-myc activation following Ras/MEK/ERK signaling pathway, which involved in the biological effects of miR-27a-3p/BTG2 axis on gastric carcinogenesis and cancer progression. Overall, these results suggested that the miR-27a-3p/BTG2 axis might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the management of gastric cancer.
Highlights
Gastric cancer (GC) is one of the most common malignant diseases and the second leading cause of cancer-related mortalities worldwide, especially in Asian countries [1, 2]
We found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p
These data indicated that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer, while the expression level of miR-27-3p in GC was significantly higher than that of miR-27a-5p
Summary
Gastric cancer (GC) is one of the most common malignant diseases and the second leading cause of cancer-related mortalities worldwide, especially in Asian countries [1, 2]. The pathogenic mechanisms contributing to gastric carcinogenesis and cancer progression are incompletely elucidated. Understanding of this process may identify potential markers and therapeutic targets for gastric cancer. It has been demonstrated that microRNAs (miRNAs) are involved in the development of malignant disease, including gastric cancer [4, 5]. MicroRNAs are a class of diverse, small, non-coding RNAs of 21–25 nucleotides in length that result in translational repression or degradation through targeting complementary sequences of mRNAs in the 3’-untranslated region (3’-UTR) and regulate a wide range of physiological and pathological processes including www.impactjournals.com/oncotarget cell proliferation, differentiation, motility, apoptosis, angiogenesis and metastasis. Accumulated evidence indicates that miRNAs are aberrantly expressed in human cancers and may function as tumor suppressors or oncogenes [6]
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