Original ResearchFull Report: Basic and Translational—Alimentary TractGenetic and Epigenetic Down-regulation of MicroRNA-212 Promotes Colorectal Tumor Metastasis via Dysregulation of MnSOD
Section snippets
Materials and Methods
The Materials and Methods can be found in the Supplementary Material.
Reduced miR-212 Is Frequently Detected in CRC Cell Lines and Tissues
We first detected the expression of miR-212 in colorectal cell lines and 30 pairs of tissue samples (tumors and normal). All 5 CRC cell lines presented lower miR-212 expression than the normal intestinal epithelial cell line FHC19 (P < .01; Figure 1A). In addition, among 30 CRC tumor tissue samples, 24 (80%) had lower miR-212 compared with the paired normal colorectal tissues (P < .05; Figure 1B).
Exogenetic Overexpression of miR-212 Suppresses CRC Cell Colony Formation, Migration, and Invasion In Vitro
To investigate the potential biological functional role of miR-212 in CRC tumorigenesis and
Discussion
In this study, we determined that miR-212 regulates the metastasis and EMT of CRC by targeting MnSOD. Several lines of evidence support our conclusion and model. First, in functional studies, introduction of miR-212 significantly repressed CRC colony formation, independent growth, migration, and invasion in vitro (Figure 1), as well as the ability to metastasize to the lung and liver in vivo (Figure 3). We did not detect significant growth inhibition in CRC cells within 72 hours (data not
Acknowledgments
The authors thank Jiemin Chen and Ling Zhou (Sun Yat-Sen University, Guangzhou, PR China) for their technical assistance. The authors thank Xinyuan Guan (The University of Hong Kong, Hong Kong, PR China) for the synthesis of fluorescence in situ hybridization probe.
Hui Wang’s Current address is: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, PR China; Yufang Zuo's Current address: Cancer Center,
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Author names in bold designate shared co-first authorship.
Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by grants from the National High Technology Research and Development Program of China (project 863, no. 2012AA02A204), the National Basic Research Program of China (973 Program, no. 2011CB504805, 2010CB912201, 2010CB529904), the National Natural Science Foundation of China (no. 81272638, 30973448) and Guangdong Innovative Research Team Program (no. 2009010058).