Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer
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Colorectal cancer (CRC) has a high prevalence and mortality rate. Biomarkers for predicting the recurrence of CRC are not clinically available. This study investigated the role of circulating miR-15b in the prediction of CRC recurrence and the associated mechanism. miR-15b levels in plasma and tissues were measured by real-time PCR. Metastasis suppressor-1 (MTSS1) and Klotho protein expression were detected by Western blot and immunohistochemistry. Invasion and migration of CRC tumor cells were measured by transwell plates. Liver metastasis was established by intraspleen injection of HCT116 cells. Plasma miR-15b levels were significantly higher in CRC patients than in healthy controls, in CRC patients with metastasis than in CRC patients without metastasis, and in CRC patients with recurrence than in CRC patients without recurrence in the 5-year follow-up. miR-15b level in CRC tumors was significantly higher than that in peritumoral tissues. High plasma miR-15b level and negative MTSS1 and Klotho expression in tumor tissues significantly correlated with poor survival. Inhibition of miR-15b activity by adenovirus carrying antimiR-15b sequence significantly increased MTSS1 and Klotho protein expression and subsequently decreased colony formation ability, invasion, and migration of HCT116 cells in vitro and liver metastasis of HCT116 tumors in vivo. In conclusion, high abundance of circulating miR-15b correlated with tumor metastasis, recurrence, and poor patient prognosis through downregulation of MTSS1 and Klotho protein expression.
KeywordsColorectal cancer Metastasis miR-15b Prognosis MTSS1 Klotho
This study was supported by the National 863 Hi-tech Project of China (2007AA021803, 2007AA021901, 2007AA021809, 2007AA021811), the National Natural Science Foundation of China (81272972), National Basic Research Program of China (2010CB833605), Hunan Provincial Science and Technology Department (2010FJ4030), Incubation Program for National Natural Science Funds for Distinguished Young Scholar of Central South University (2010QYZD006), and Open-End Fund for the Valuable and Precision Instruments of Central South University.
Compliance with ethical standards
This study was approved by the Ethics Committee for Human Research of Xiangya Hospital. The animal protocol was preapproved by Central South University, and all experiments were performed in accordance to the animal care guidelines of the Chinese Council.
Conflicts of interest
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