Abstract

Zhennan Li^†,

Xiaodong Wang,

Peng Xu,

Long Zhao and

Jianjun Qian

^† These authors contributed equally to this work.

Abstract  Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly human malignant diseases and the sixth leading cause of cancer-related deaths in China. Gemcitabine is the only first-line chemotherapeutic agent used for the palliative treatment of patients with PDAC, but chemo-resistance limits their efficacy. Here, we showed that miR-125a was up-regulated in chemo-resistant SW1990GZ cells when compared with SW1990 cells. Over-expression of miR-125a increased the chemo-resistance to gemcitabine in SW1990 cells, while down-regulation of miR-125a in SW1990GZ cells increased chemo-sensitivity to gemcitabine. By using bioinformatics analysis tool (Targetscan), the 3′ untranslated region (3′UTR) of A20 gene was found to be a target of miR-125a. Luciferase reporter assay further confirmed that A20 3′UTR is a direct target of miR-125a. Over-expression of A20 in SW1990 cells increased chemo-sensitivity to gemcitabine, while knockdown of A20 in SW1990 cells promoted the chemo-resistance to gemcitabine. Finally, the expression level of miR-125a in pancreatic cancer tissues from chemo-sensitive patients was significantly lower than that from chemo-resistant patients, and was inversely correlated with the A20 mRNA levels. In conclusion, our results suggest that miR-125a promotes chemo-resistance to gemcitabine in pancreatic cells through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.

Keywords   PDAC; gemcitabine; miR-125a; A20; chemo-resistance

Received   2015-7-23　　

Accepted  2015-9-29

Funding  This work was supported by the grant from the National Natural Science Foundation of China (No. 81272715).

* Correspondence address  Tel: +86-514-87373012; Fax: +86-514-87373022; E-mail: [email protected]