miRNA is an important regulator of gene expression at the post-transcriptional level and participates in cell development, differentiation, proliferation, cell-cycle control, apoptosis, and metabolism [
4]. Increased evidences have implied that miRNAs function as oncogene and tumor-suppressor genes, regulating the expression and function of their related target genes during the biological process of cancer cells. Our previous study showed that there was distinct miRNA profiling between GC tissues and matched non-tumor tissues based on the miRNA microarray analysis (Additional file
4: Table S4). In the present study, miR-29a-3p was selected as a candidate miRNA due to its down-regulation in tumor tissues. miR-29a-3p is one of the members of miR-29 family, which also includes miR-29b and miR-29c. Accumulating evidences have shown that the aberrant expression of miR-29s are prevalent in multiple cancer types and are involved in complex regulatory process by targeting multiple factors associated with several common pathways, indicating its critical role in carcinogenesis and cancer progression [
14-
18]. miR-29a has two different transcripts, which are miR-29a-3p and miR-29a-5p, respectively. Neither of them has been reported specific aberrant expression in tumors. Recent studies have found that miR-29a is up-regulated in indolent human B cell chronic lymphocytic leukemia (B-CLL) and acute myeloid leukemia (AML) [
19,
20]. However, some researches reveal that miR-29a is down-regulated in neuroblastoma, sarcomas, and brain tumors [
12,
21]. In fact, miR-29a could suppress cell proliferation and induce cell-cycle arrest
via the down-regulation of p42.3 expression [
22]. These inconsistent findings indicate that dysregulation of miR-29a in various cancers may be dependent on the cellular microenvironment, especially with regard to detecting different transcripts of miR-29a-3p. In the present study, we analyzed the expression levels of miR-29a-3p transcript in GC tissue samples and GC cells and its primary biological function on GC cells. We found that decreased expression of miR-29a-3p in GC tumor tissues was related to the degree of cell differentiation. Decreased miR-29a-3p expression promoted gastric cancer cell proliferation
via reducing the expression of cell-cycle regulators including: CDK2, CDK4, and CDK6. In a way, our finding might be consistent with the reporting of Cui Y
et al. [
22].
Many miRNAs have been identified as key players in metastasis and invasion process of tumor. In prostate cancer, miR-29a is considered as a putative tumor-suppressive miRNA, contributing to cell migration and invasion [
23]. miR-29 family plays a dominant role in regulating extracellular matrix genes, such as collagens, LAMA2, integrin β, Mmp2, fibrillin, secreted protein, acidic, and Sparc [
16,
24], consequently contributing to the promotion of cancer cell migration and metastasis. The present findings showed that miR-29a-3p significantly inhibits the cell invasion and migration ability in GC cells. With the help of bioinformatics prediction (Target scan, miRanda, miRWalk, and miRDB),
ITGA6,
LAMA2, and
DNMT3A were identified as direct targets of miR-29a-3p. Thus, the function of miR-29a-3p in metastasis depends on its target regulation. Although we evaluated its potential target gene
ITGA6,
LAMA2 expression in miR-29a-3p mimic, and inhibitor-transfected cells (Additional file
5: Figure S5), future studies should be required to validate the association between miR-29a-3p and targets. These results indicate that miR-29a-3p may serve as a potential predictor for prognosis of gastric cancer patients.