Rho GDP-dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer.
Rho GDP-dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer.
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Rho GDP 解离抑制剂 α 是一种潜在的预后生物标志物，可控制结直肠癌的端粒调节
DOI：
10.1111/cas.13259
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发表时间：
2017-07
期刊：
影响因子：
5.7
通讯作者：
Fang L
中科院分区：
文献类型：
--
作者：
Huang D;Lu W;Zou S;Wang H;Jiang Y;Zhang X;Li P;Songyang Z;Wang L;Wang J;Huang J;Fang L
Rho GDP-解离抑制剂α（RhoGDIα）是Rho GTP酶的重要调节剂。虽然RhoGDIα可能是结直肠癌（CRC）的一个癌基因，但其潜在机制尚不清楚。我们研究了RhoGDIα在结直肠癌进展中的作用、机制和临床意义。我们发现RhoGDIα的下调抑制了CRC细胞的增殖、运动和侵袭。RhoGDIα的过表达增加了端粒DNA损伤反应信号，并导致CRC细胞中的端粒缩短，这也在26对CRC组织中得到验证。机制研究表明，RhoGDIα可通过磷脂酰肌醇3-激酶-蛋白激酶B信号通路促进端粒重复因子1（TRF 1）的表达。此外，RhoGDIα蛋白水平与结直肠癌组织中的TRF 1密切相关。297例结直肠癌样本的队列验证了RhoGDIα和TRF 1之间的正相关性，并显示RhoGDIα和TRF 1水平与结直肠癌患者的生存率呈负相关。综上所述，我们的研究结果表明，RhoGDIα调节TRF 1和端粒长度，可能是结直肠癌的新的预后生物标志物。
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.