Abstract
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.
Highlights
Gastric cancer is the fourth most prevalent cancer and the second most frequent cause of cancer-related mortalities in the world, accounting for more than 720,000 deaths annually [1, 2]
MiRNA plays a regulatory role in inhibition of protein expression and altered expression of miRNAs was associated with cancer development and progression [14, 15].In the current study, we found that miR-31 expression was down-regulated in gastric cancer tissues and cell lines, while down-regulation of miR-31 expression associates with clinicopathological characteristics and prognosis of gastric cancer patients
MiR-31 antitumor activity was through targeting of E2F2 expressionin gastric cancer cells
Summary
Gastric cancer is the fourth most prevalent cancer and the second most frequent cause of cancer-related mortalities in the world, accounting for more than 720,000 deaths annually [1, 2]. More than 70% of gastric cancer occurs in the developing world [3] and gastric cancer new case and mortality were the highest in China according to the WHO world cancer report 2014. Tumor cell-unlimited proliferation and strong invasive and metastasis ability are the main causes of high malignancy degree and worse overall survival. Identification of molecular aberrations that can predict tumor progression and survival rate might lead to creating a novel diagnostic means and thereby improving prognosis of gastric cancer
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