Modulation of tumorigenesis by the pro-inflammatory microRNA miR-301a in mouse models of lung cancer and colorectal cancer

促炎性 microRNA miR-301a 在肺癌和结直肠癌小鼠模型中对肿瘤发生的调节

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作者:Xiaodong Ma, Fang Yan, Qipan Deng, Fenge Li, Zhongxin Lu, Mofang Liu, Lisheng Wang, Daniel J Conklin, James McCracken, Sanjay Srivastava, Aruni Bhatnagar, Yong Li

Abstract

Lung cancer and colorectal cancer account for over one-third of all cancer deaths in the United States. MicroRNA-301a (miR-301a) is an activator of both nuclear factor-κB (NF-κB) and Stat3, and is overexpressed in both deadly malignancies. In this work, we show that genetic ablation of miR-301a reduces Kras-driven lung tumorigenesis in mice. And miR-301a deficiency protects animals from dextran sodium sulfate-induced colon inflammation and colitis-associated colon carcinogenesis. We also demonstrate that miR-301a deletion in bone marrow-derived cells attenuates tumor growth in the colon carcinogenesis model. Our findings ascertain that one microRNA-miR-301a-activates two major inflammatory pathways (NF-κB and Stat3) in vivo, generating a pro-inflammatory microenvironment that facilitates tumorigenesis.

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