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Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
Authors:Dandan Huang  Weisi Lu  Shaomin Zou  Huaiming Wang  Yuanling Jiang  Xiya Zhang  Pengqing Li  Zhou Songyang  Lei Wang  Jianping Wang  Junjiu Huang  Lekun Fang
Affiliation:1. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat‐sen University, Guangzhou, China;2. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat‐sen University, Guangzhou, China;3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‐sen University, Guangzhou, China;4. Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat‐sen University, Guangzhou, China
Abstract:Rho GDP‐dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα could promote telomeric repeat factor 1 (TRF1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.
Keywords:Colorectal cancer  prognosis  RhoGDIα    telomere  TRF1
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