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MiR-203 regulates JAK-STAT pathway in affecting pancreatic cancer cells proliferation and apoptosis by targeting SOCS3.

Abstract：

OBJECTIVE:Janus kinase (JAK)- signal transducer and transcriptional activator (STAT) pathway overactivation is closely related to tumorigenesis. Cytokine signal transduction inhibitor 3 (SOCS3) is a negative regulator of JAK-STAT. It is shown that miR-203 is significantly elevated in the pancreatic cancer tissues. The bioinformatics analysis revealed a targeted binding site between miR-203 and the 3'-UTR of SOCS3 mRNA. This study investigated the role of miR-203 in regulating SOCS3 expression and the proliferation and apoptosis of the pancreatic cancer cells. PATIENTS AND METHODS:Quantitative Real Time-PCR (qRT-PCR) was used to detect the expressions of miR-203 and SCOS3 mRNA in tumor tissues and paracancerous tissues. The Dual-Luciferase reporter gene assay was adopted to validate the target interaction between miR-203 and SOCS3. The PANC-1 cells were cultured in vitro and divided into miR-NC group and miR-203 inhibitor group followed by an analysis of the expressions of SOCS3, p-JAK2, and p-STAT3, cell apoptosis by flow cytometry, and cell proliferation by EdU staining. RESULTS:Compared with the adjacent tissues, miR-203 expression was significantly increased, while SOCS3 mRNA level was significantly declined in the tumor tissues of pancreatic cancer patients. There was a targeted regulatory relationship between miR-203 and SOCS3 mRNA. Compared with those in HPDE6-C7 cells, miR-203 level was upregulated, whereas SOCS3 mRNA and the protein expressions were reduced in pancreatic cancer PANC-1 and BXPC3 cells. The transfection of miR-203 inhibitor significantly increased SOCS3 mRNA and the protein levels, decreased p-JAK2 and p-STAT3 protein expressions, enhanced cell apoptosis, and inhibited cell proliferation in the pancreatic cancer PANC-1 cells. CONCLUSIONS:Increased miR-203 expression and reduced SOCS3 level are associated with the pathogenesis of pancreatic cancer. MiR-203 can regulate the proliferation and apoptosis of the pancreatic cancer cells by targeting the inhibited SOCS3 expression and regulating the JAK-STAT pathway activity.

journal_name

Eur Rev Med Pharmacol Sci

journal_title

European review for medical and pharmacological sciences

authors

Lin XM,Chen H,Zhan XL

doi

10.26355/eurrev_201908_18730

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

6906-6913

issue

eissn

1128-3602

issn

2284-0729

journal_volume

pub_type

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MiR-203 regulates JAK-STAT pathway in affecting pancreatic cancer cells proliferation and apoptosis by targeting SOCS3.