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NMI promotes cell proliferation through TGFβ/Smad pathway by upregulating STAT1 in colorectal cancer
Authors:Dongjian Ji  Yifei Feng  Wen Peng  Jie Li  Qi’ou Gu  Zhiyuan Zhang  Wenwei Qian  Qingyuan Wang  Yue Zhang  Yueming Sun
Institution:1. The First College of Clinical Medicine, Nanjing Medical University, Nanjing, P.R. China;2. Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China

Dongjian Ji, Yifei Feng and Wen Peng contributed equally to this work.;3. The First College of Clinical Medicine, Nanjing Medical University, Nanjing, P.R. China

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China

Dongjian Ji, Yifei Feng and Wen Peng contributed equally to this work.;4. The First College of Clinical Medicine, Nanjing Medical University, Nanjing, P.R. China

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China;5. Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China

Abstract:Colorectal cancer (CRC) is still a fatal health problem around the world. The underlying mechanisms of CRC have not been fully elucidated. N-myc interactor (NMI) acts as an oncogene or a tumor-suppressor gene in several kinds of cancers but CRC. Here, the expression of NMI was found higher in CRC tissues and cells. Higher expression of NMI indicated the poorer prognosis of CRC patients. Moreover, the proliferation of CRC cells was suppressed significantly after we silenced the expression of NMI, while overexpression of NMI promoted CRC cell proliferation. Flow cytometry demonstrated that NMI promoted cell proliferation through facilitating cell transition from the G1 phase to the S phase. Furthermore, it was found that NMI suppressed the phosphorylation of Smad3 by upregulating the expression of STAT1. The effect of NMI depletion on cell proliferation could be reversed by using Smad3 inhibitor SIS3. In summary, our findings demonstrated that NMI promoted cell proliferation via TGFβ/Smad pathway and could indicate the prognosis of patients with CRC.
Keywords:cell proliferation  colorectal cancer  N-myc interactor  STAT1  TGFβ/Smad pathway
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