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Tazarotene-induced gene 1 interacts with Polo-like kinase 2 and inhibits cell proliferation in HCT116 colorectal cancer cells
Authors:Chun-Hua Wang  Tzung-Ju Lu  Lu-Kai Wang  Chang-Chieh Wu  Mao-Liang Chen  Chan-Yen Kuo  Rong-Yaun Shyu  Fu-Ming Tsai
Affiliation:1. Department of Dermatology, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan

School of Medicine, Tzu Chi University, Hualien, Taiwan;2. School of Medicine, Tzu Chi University, Hualien, Taiwan

Division of Colon and Rectal Surgery, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan;3. Radiation Biology Core Laboratory, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Taoyuan, Taiwan;4. Department of Surgery, Tri-Service General Hospital Keelung Branch, National Defense Medical Center, Keelung, Taiwan;5. Department of Research, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan;6. Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan

Abstract:Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2.
Keywords:cell proliferation  cyclin E1  Fbxw7  Polo-like kinases  tazarotene-induced gene 1
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