miR-574-5p negatively regulates Qki6/7 to impact β-catenin/Wnt signalling and the development of colorectal cancer
- Shunlong Ji1,
- Gengtai Ye2,
- Jun Zhang1,
- Linpei Wang2,
- Tao Wang1,
- Zhen Wang1,
- Tiantian Zhang1,
- Guanghui Wang1,
- Zongsheng Guo1,
- Yu Luo3,
- Jianchun Cai2,
- James Y Yang1,4
- 1State Key Laboratory of Cellular Stress Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China
- 2Department of Surgical Oncology the First Affiliated Hospital of Xiamen University and Xiamen Cancer Center, Xiamen, People's Republic of China
- 3School of Nursing, the Third Military Medical University, Chongqing, People's Republic of China
- 4Fujian Provincial Transgenic Core, Xiamen University Laboratory Animal Center, Xiamen, People's Republic of China
- Correspondence to Dr James Y Yang, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiamen, China 361005; or Dr Jianchun Cai, Department of Surgical Oncology, the First Affiliated Hospital of Xiamen University and Xiamen Cancer Center, Xiamen, China 361003;
Contributors SJ, GY, JZ, LW, TW, ZW, TZ and GW performed the experiments, collected and analysed the data; YL and ZG designed the experiments, analysed the data and revised the paper; JC designed and supervised the project, analysed the data and revised the paper; JYY conceived, designed and supervised the project, analysed the data, wrote and revised the paper.
- Revised 16 January 2012
- Accepted 2 February 2012
- Published Online First 5 April 2012
Objective Deficiency or reduced expression of signal transduction and activation of RNA family protein Quaking (Qki) is associated with developmental defects in neural and vascular tissues and the development of debilitating human diseases including colorectal cancer (CRC). However, the mechanisms underlying the aberrant downregulation or deficiency of Qki were uncertain.
Design Expression of miR-574-5p, Qki5/6/7/7b splicing variants, β-catenin and p27Kip1 was determined in mouse and human CRC cells and tissues to investigate the post-transcriptional regulation of Qki isoforms by miR-574-5p and its impact on β-catenin/p27Kip1 signalling, cell cycle progression, proliferation, migration, invasion and tumour growth.
Results In the CRC tissues of C57BL/6-Apcmin/+ mice, miR-574-5p was found to be significantly upregulated and negatively correlated with the expression of Qki but positively correlated with the expression of β-catenin. In mouse and human CRC cells, miR-574-5p was shown to regulate Qki isoforms (Qki6/7 in particular) post-transcriptionally and caused altered expression in β-catenin and p27Kip1 , increased proliferation, migration and invasion and decreased differentiation and cell cycle exit. Furthermore, in clinical CRC tissues, miR-574-5p was shown to be greatly upregulated and inversely correlated with the expression of Qkis. Finally, inhibition of miR-574-5p was shown to suppress the growth of tumours in the nude mice.
Conclusions Together, these novel findings suggest that miR-574-5p is a potent ribo-regulator for Qkis and that aberrant miR-574-5p upregulation can be oncogenic.
- colorectal cancer
- abdominal surgery
- hepatic encephalopathy
- gut inflammation
- colorectal cancer
- cell biology
- colorectal cancer genes
- gene mutation
SJ, GY and JZ contributed equally to the work.
Funding This work was supported in part by grants from the National Science Foundation of China (30970649), the 973 Program of China (2009CB941601), the Fujian Provincial Department of Science and Technology (2010L0002), and the 111 Project of Education of China (B06016).
Competing interests None.
Ethics approval Institutional Medical Ethics Committee of Xiamen University.
Provenance and peer review Not commissioned; externally peer reviewed.
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