MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3

J. Xie, J.-T. Wen, X.-J. Xue, K.-P. Zhang, X.-Z. Wang, H.-H. Cheng

Department of Radiotherapy, Xingtai People’s Hospital, Xingtai, Hubei, China. xiaozhenwanguy@sina.com

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• Oncology

OBJECTIVE: The over-activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway induced by cytokines are closely correlated with tumorigenesis. Suppressor of cytokine signaling 3 (SOCS3) serves as a negative regulator for JAK-STAT, and its down-regulation is involved in the oncogenesis of pancreatic cancer. We aimed at investigating the effect of miR-221 on the expression and proliferation, cycle and apoptosis of pancreatic cancer cells and determine the related mechanism.

PATIENTS AND METHODS: Dual luciferase reporter gene assay was used to analyze the regulation between miR-221 and SOCS3. The expressions of miR-221, SOCS3, p-JAK and p-STAT3 in normal human pancreatic epithelial cell HPDE6-C7 and pancreatic cancer cell PANC-1 were quantified by qPCR and Western blot. Flow cytometry was used to identify cell cycle and proliferation. In vitro cultured PANC-1 cells were transfected with miR-221 inhibitor or pIRES2-SOCS3. The expressions of miR-221, SOCS3, p-JAK and p-STAT3, along with the cell proliferation or apoptosis, were compared.

RESULTS: Bioinformatics analysis showed the existence of binding site between miR-221 and 3’-UTR of SOCS3 mRNA. Dual luciferase gene reporter assay confirmed the targeted regulation between miR-221 and SOCS3. Compared to HPDE6-C7 cells, higher levels of miR-221, p-JAK and p-STAT3 expression, and lower expression of SOCS3, were found in PANC-1 cells, along with the increase of cell proliferation. Transfection of miR-221 inhibitor or pIRES2-SOCS3 remarkably enhanced SOCS3 expression, inhibited the levels of p-JAK and p-STAT3 expression, and impeded the proliferation of PANC-1 cells.

CONCLUSIONS: MiR-221 decreases proliferation potency of PANC-1 cells and affects JAK-STAT3 signaling pathway via inhibiting SOCS3.

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