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MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2

Abstract

Background

Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC.

Methodology

Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3′UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells.

Results

miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells.

Conclusions

This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.

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Acknowledgments

Dr. Ren X.L., He G.Y., Li X.M., Yi L.Z. and Lu G.F. carried out experiments. Dr. Xin S.N., Wu P.X. and Li Y.L. took on the statistical analysis. Ren X.L., He G.Y. and Li X.M. contributed equally to this work. Professor Liao WT gave assistance in collecting tissue samples or animal experiments. Professor Ding Y.Q. and Liang L. conceived experiments and analyzed data. All authors were involved in writing the paper and had final approval of the submitted and published versions. We thank Professor Geevan and Reddy for editing the English writing.

Funding

This work was supported by the National Natural Science Foundation of China (81272759, 81172382, 81472313), National Basic Research Program of China (973 Program, 2015CB554002), the Science and Technology Planning Project of Guangdong Province (S2013010014544), Major projects of science and technology of Guangzhou (201300000056) and the Key Project of National Natural Science Fund (Guangdong Province NSFC-Joint Fund, U1201226).

Author information

Correspondence to L. Liang.

Ethics declarations

All protocols for animal studies were reviewed and approved by the Institutional Animal Care and Use Committee of Southern Medical University and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Conflict of interest

All the authors declare that they have no conflict of interest.

Additional information

X. L. Ren, G. Y. He and X. M. Li have contributed equally to this work.

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Ren, X.L., He, G.Y., Li, X.M. et al. MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2. J Cancer Res Clin Oncol 142, 581–592 (2016). https://doi.org/10.1007/s00432-015-2053-8

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Keywords

  • MiR-206
  • Colorectal cancer
  • Progression
  • FMNL2