期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 119, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109424
关键词
miR-143-3p; KRAS; Proliferation; Metastasis; PDAC
资金
- State Key Scientific and Technological Research Programs, China [2017ZX10203207-003-0020]
- Science and Technological Supports Project of Sichuan Province [2018SZ0204, 2019YJ0149]
- Health and Family Planning Commission of Sichuan Province [17PJ393]
- Science and Technology Project of Chengdu [2018-YF0501460-SN]
Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with high mortality and metastasis, which is difficult to diagnose and treat. MicroRNA-143-3p (miR-143-3p) acts as a tumor suppressor in various cancers. However, its role in pancreatic ductal adenocarcinoma has not been explored. Here we examined the potential role and mechanism of miR-143-3p in PDAC. Methods: The levels of miR-143-3p and KRAS mRNA in matched PDAC and normal tissues as well as PDAC cell lines were determined by quantitative RT-PCR. The effect of miR-143-3p on cell proliferation was evaluated by Cell Counting Kit-8 assay, colony-forming assay and a mouse subcutaneous transplantation model. Transwell assay, wound healing assay and a mouse orthotopic implantation model were conducted to examine the role of miR-143-3p on cell migratory and invasive capacities. The target gene and mechanisms of miR-143-3p were explored by qRT-PCR, western blot and luciferase assays. Results: The expression of miR-143-3p was down-regulated in PDAC tissues compared with the paired adjacent normal tissues. Cell proliferative, migratory and invasive capacities in PDAC cells were significantly decreased by miR-143-3p up-regulation. Moreover, we identified KRAS as a direct target of miR-143-3p, revealed its expression to be inversely correlated with miR-143-3p in PDAC samples. Up-regulated expression of KRAS partially reversed the phenotypes induced by miR-143-3p overexpression. What's more, KRAS could activate the ERK signaling pathway, which is associated with tumorigenesis. Conclusions: MiR-143-3p may suppress tumorigenesis in PDAC by targeting KRAS. This might provide a theoretical basis for miR-143-3p in treatment of pancreatic cancer.
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