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Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma

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Abstract

Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.

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Acknowledgments

The authors wish to thank Prof. Rui Wang and Dr. Ming Sun for their technical support and sincere help.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, First Hospital Affiliated to the Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing, 100048, China

    Zi-Man Zhu, Jun-Dong Du, Xiang-Long Tan , Yu-Liang Tu, Jing-Wang Tan & Hua-Bao Jiao

  2. Department of Pharmacy, First Hospital Affiliated to the Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing, 100048, China

    Yue-Fang Xu

  3. Department of Pathology, Lanzhou Military Area General Hospital, Lanzhou, 730050, China

    Qin-Jun Su

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  1. Zi-Man Zhu
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  2. Yue-Fang Xu
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  5. Xiang-Long Tan
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Correspondence to Hua-Bao Jiao.

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Zi-Man Zhu, Yue-Fang Xu and Qin-Jun Su should be regarded as joint first authors for their equal contributions.

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Zhu, ZM., Xu, YF., Su, QJ. et al. Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma. Mol Cell Biochem 388, 39–49 (2014). https://doi.org/10.1007/s11010-013-1897-y

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  • DOI: https://doi.org/10.1007/s11010-013-1897-y

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