Decreased expression of miR-551b predicts poor prognosis and promotes tumorigenesis by targeting PTP4A3 in human colorectal cancer

H.-Y. Sun, Z.-C. Qu, D.-M. Liu, W. Zhang, G. Liu, L. Zhu

Department Gastroenterology, Dongzhimen Hospital Beijing University of Chinese Medicine, Dongcheng, Beijing, China. xhmmlak7741@sina.com

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• Oncology

OBJECTIVE: MiR-551b has been reported to display tumor-suppressive and oncogenic potential in several cancers, but there has been no study on the roles of miR-551b in colorectal cancer (CRC). In this work, we aimed to explore the potential functions and mechanisms of miR-551b in the modulation of the CRC progression.

PATIENTS AND METHODS: The expressions of miR-551b were examined in 122 pairs of CRC cancer tissues and adjacent non-tumor samples by Real Time-Polymerase Chain Reaction (RT-PCR). The clinical significance of miR-551b in CRC patients was explored using a Chi-square test, Kaplan-Meier assays, and multivariate analysis. MiR-551b mimics and inhibitors were used to establish miR-551b upregulation and downregulation models in CRC cells to examine the functions of miR-551b on cells proliferation, migration, invasion, and apoptosis. Dual-luciferase reporter assays were conducted for the validation of the possible modulation of a putative target of miR-551b.

RESULTS: We showed that miR-551b was significantly down-regulated in CRC tissues and cell lines. It was observed that miR-551b expressions were correlated with lymph nodes metastasis, TNM stage, and poor prognosis. Multivariate analysis identifies low level of miR-551b expressions as an independent predictor for a shorter overall survival. The functional assessment suggested that forced miR-551b expression distinctly suppressed CRC cells growth, invasion, and migration, while the suppression of miR-551b displayed the opposite trend. Mechanistic studies confirmed that PTP4A3 was identified as a direct target of miR-551b in CRC. Interesting observations revealed that the cells capacities were higher in miR-551b +PTP4A3 group, when compared with those in miR-551b group, indicating that up-regulation of PTP4A3 rescued the repressive functions of miR-551b overexpression on CRC cells growth and migration.

CONCLUSIONS: The findings of our study first showed that miR-551b, a potential tumor suppressor, may be used as a promising prognostic predictor and therapeutic target for CRC.

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