The miRNA microarray analysis showed that miR-31 was reduced in gastric cancer. This study further assessed miR-31 expression and role of miR-31 in gastric cancer tissues and cell lines. The data showed that miR-31 expression was down-regulated in 40 cases of gastric cancer tissues compared to the adjacent normal tissues, and low expression of miR-31 was associated with poor tumor differentiation, lymph node metastasis, advanced T stage and worse overall survival of gastric cancer patients. Ectopic expression of miR-31 reduced tumor cell viability, enhanced apoptosis, arrested tumor cells at G1 transition, and reduced tumor cell migration and invasion in SGC-7901 and MGC-803 gastric cell lines in vitro. Enforced expression of miR-31 also inhibited growth of engrafted tumors in vivo. Luciferase reporter assays and western blot revealed that E2F2 is the direct target of miR-31. E2F2 expression was upregulated in gastric cancer tissues, and inversely associated with miR-31 levels, while knockdown of E2F2 expression mimicked miR-31 anti-tumor activity in gastric cancer cells, but the ectopic expression of E2F2 rescued the miR-31-mediated inhibition in gastric cell lines. Taken together, these results demonstrated that miR-31 acts as a crucial tumor suppressive activity by inhibiting E2F2s expression. Thus, miR-31 might be a candidate therapeutic target for gastric cancer patients.
Gene expression is regulated at the transcription and translation levels; thus, both transcription factors (TFs) and microRNAs (miRNA) play roles in regulation of gene expression. This study profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues to construct a TF and miRNA co-regulatory network in order to identify altered genes in gastric cancer progression. A total of 70 cases gastric cancer and paired adjacent normal tissues were subjected to cDNA and miRNA microarray analyses. We obtained 887 up-regulated and 93 down-regulated genes and 41 down-regulated and 4 up-regulated miRNAs in gastric cancer tissues. Using the Transcriptional Regulatory Element Database, we obtained 105 genes that are regulated by the E2F family of genes and using Targetscan, miRanda, miRDB and miRWalk tools, we predicted potential targeting genes of these 45 miRNAs. We then built up the E2F-related TF and miRNA co-regulatory gene network and identified 9 hub-genes. Furthermore, we found that levels of E2F1, 2, 3, 4, 5, and 7 mRNAs associated with gastric cancer cell invasion capacity, and has associated with tumor differentiation. These data showed Overexpression of E2F mRNAs associated with gastric cancer progression.
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