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Inhibition of autophagy and tumor growth in colon cancer by miR-502

Oncogene volume 32, pages 1570–1579 (2013)Cite this article

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Abstract

Autophagy is a catabolic process that allows cellular macromolecules to be broken down and recycled as metabolic precursors. The influence of non-coding microRNAs in autophagy has not been explored in colon cancer. In this study, we discover a novel mechanism of autophagy regulated by hsa-miR-502-5p (miR-502) by suppression of Rab1B, a critical mediator of autophagy. A number of other miR-502 suppressed mRNA targets (for example, dihydroorotate dehydrogenase) are also identified by microarray analysis. Ectopic expression of miR-502 inhibited autophagy, colon cancer cell growth and cell-cycle progression of colon cancer cells in vitro. miR-502 also inhibited in-vivo colon cancer growth in a mouse tumor xenografts model. In addition, the expression of miR-502 was regulated by p53 via a negative feedback regulatory mechanism. The expression of miR-502 was downregulated in colon cancer patient specimens compared with the paired normal control samples. These results suggest that miR-502 may function as a potential tumor suppressor and therefore be a novel candidate for developing miR-502-based therapeutic strategies.

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Acknowledgements

We appreciate the critical review by Ms Sonya R Lorrain. We thank Dr Stella E Tsirka for technical support in animal experiments. This study was supported in part by Stony Brook University Translational Research Laboratory Start-up Fund (J Ju), R01CA155019 (J Ju) and R33CA147966 (J Ju).

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Authors and Affiliations

  1. Department of Pathology, Translational Research Laboratory, Stony Brook University, Stony Brook, NY, USA

    H Zhai & J Ju

  2. Department of Pathology, Dalian Medical University, Dalian, China

    B Song

  3. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA

    X Xu & W Zhu

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Zhai, H., Song, B., Xu, X. et al. Inhibition of autophagy and tumor growth in colon cancer by miR-502. Oncogene 32, 1570–1579 (2013). https://doi.org/10.1038/onc.2012.167

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