Open AccessRho GDP ‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
Author(s) -
Huang Dandan,
Lu Weisi,
Zou Shaomin,
Wang Huaiming,
Jiang Yuanling,
Zhang Xiya,
Li Pengqing,
Songyang Zhou,
Wang Lei,
Wang Jianping,
Huang Junjiu,
Fang Lekun
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13259
Subject(s) - colorectal cancer , telomere , kinase , cancer research , oncogene , downregulation and upregulation , biology , cancer , phosphatidylinositol , motility , cell cycle , microbiology and biotechnology , genetics , dna , gene
Rho GDP ‐dissociation inhibitor α (Rho GDI α) is an essential regulator for Rho GTP ases. Although Rho GDI α may serve as an oncogene in colorectal cancer ( CRC ), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of Rho GDI α in CRC progression. We founded that downregulation of Rho GDI α repressed CRC cell proliferation, motility, and invasion. Overexpression of Rho GDI α 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 Rho GDI α could promote telomeric repeat factor 1 ( TRF 1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, Rho GDI α protein levels were strongly correlated with TRF 1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between Rho GDI α and TRF 1, and revealed that Rho GDI α and TRF 1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that Rho GDI α regulate TRF 1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.