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Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2.

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.

SUBMITTER: Wang H

PROVIDER: S-EPMC5095022 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2.

Wang Huaidong H Zhang Xiaotian X Liu Yuxin Y Ni Zhaohui Z Lin Yan Y Duan Zipeng Z Shi Yue Y Wang Guoqing G Li Fan F

Oncotarget 20160601 24

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. Ecto ...[more]

PMID: 27174918

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Project description:BACKGROUND:Crohn's disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity. METHODS:We performed small RNA sequencing of adult colon tissue from CD and NIBD controls. Colonic epithelial cells and immune cells were isolated from colonic tissues, and microRNA-31 (miR-31) expression was measured. miR-31 expression was measured in colonoid cultures generated from controls and patients with CD. We performed small RNA-sequencing of formalin-fixed paraffin-embedded colon and ileum biopsies from treatment-naive pediatric patients with CD and controls and collected data on disease features and outcomes. RESULTS:Small RNA-sequencing and microRNA profiling in the colon revealed 2 distinct molecular subtypes, each with different clinical associations. Notably, we found that miR-31 expression was a driver of these 2 subtypes and, further, that miR-31 expression was particularly pronounced in epithelial cells. Colonoids revealed that miR-31 expression differences are preserved in this ex vivo system. In adult patients, low colonic miR-31 expression levels at the time of surgery were associated with worse disease outcome as measured by need for an end ileostomy and recurrence of disease in the neoterminal ileum. In pediatric patients, lower miR-31 expression at the time of diagnosis was associated with future development of fibrostenotic ileal CD requiring surgeryCONCLUSIONS. These findings represent an important step forward in designing more effective clinical trials and developing personalized CD therapies. FUNDING:This work was supported by CCF Career Development Award (SZS), R01-ES024983 from NIEHS (SZS and TSF), 1R01DK104828-01A1 from NIDDK (SZS and TSF), P01-DK094779-01A1 from NIDDK (SZS), P30-DK034987 from NIDDK (SZS), 1-16-ACE-47 ADA Pathway Award (PS), UNC Nutrition Obesity Research Center Pilot & Feasibility Grant P30DK056350 (PS), CCF PRO-KIIDS NETWORK (SZS and PS), UNC CGIBD T32 Training Grant from NIDDK (JBB), T32 Training Grant (5T32GM007092-42) from NIGMS (MH), and SHARE from the Helmsley Trust (SZS). The UNC Translational Pathology Laboratory is supported, in part, by grants from the National Cancer Institute (3P30CA016086) and the UNC University Cancer Research Fund (UCRF) (PS).

Dataset Information

Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2.

Publications

Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2.

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