MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways

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MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways

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Title: MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways
Author: Yan, Xingxue; Zhu, Zhendong; Xu, Shenmin; Yang, Li-nan; Liao, Xin-Hua; Zheng, Min; Yang, Dayun; Wang, Jichuang; Chen, Dongmei; Wang, Long; Liu, Xiaolong; Liu, Jingfeng; Chen, Ruey-Hwa; Zhen Zhou, Xiao; Ping Lu, Kun; Liu, Hekun

Note: Order does not necessarily reflect citation order of authors.

Citation: Yan, X., Z. Zhu, S. Xu, L. Yang, X. Liao, M. Zheng, D. Yang, et al. 2017. “MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways.” Scientific Reports 7 (1): 45915. doi:10.1038/srep45915. http://dx.doi.org/10.1038/srep45915.
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Abstract: Hepatocellular carcinoma (HCC) is the second leading cause of cancer related-death. As a major common regulator of numerous cancer-driving pathways and a unique therapeutic target, the prolyl isomerase Pin1 is overexpressed in a majority of HCCs, whereas the mechanism underlying Pin1 overexpression remains elusive. Here we find that miR-140-5p inhibits HCC by directly targeting Pin1 to block multiple cancer-driving pathways. Bioinformatics analysis, miRNA binding and functional assays identify that miR-140-5p directly interacts with the 3′UTR of Pin1 and inhibits Pin1 translation. Furthermore, like stable Pin1 knockdown, moderate overexpression of miR-140-5p not only eliminates Pin1, but also inhibits cells growth and metastasis. Importantly, these effects of miR-140-5p are largely rescued by reconstitution of Pin1. Moreover, miR-140-5p inhibits multiple Pin1-dependent cancer pathways and suppresses tumor growth in mice. The clinical significance of these findings has been substantiated by the demonstrations that miR-140-5p is frequently down-regulated and inversely correlated with Pin1 overexpression in HCC tissues and cell lines. Given prevalent miR-140-5p downregulation in other cancers and major impact of Pin1 overexpression on activating numerous cancer-driving pathways including global miRNA downregulation, the miR-140-5p/Pin1 axis may play a major role in tumorigenesis and offer promising therapeutic targets for HCC and other cancers.
Published Version: doi:10.1038/srep45915
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382892/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630598
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