Regulation of the MicroRNA 200b (miRNA-200b) by Transcriptional Regulators PEA3 and ELK-1 Protein Affects Expression of Pin1 Protein to Control Anoikis

Zhang, Xusen; Zhang, Bailin; Gao, Jun; Wang, Xiang; Liu, Zhihua

doi:10.1074/jbc.m113.478016

Cited by 44 publications

(34 citation statements)

References 59 publications

(46 reference statements)

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“…1a) and found to be frequently downregulated in HCC145. Interestingly, in addition to a miR-200s target site, as reported2122, Pin1 3′UTR has a predicted miR-140-5p target site (Fig. 1b and c).…”

Section: Resultsmentioning

confidence: 74%

“…Such pin1-catalysed conformational regulation, which can be detected by cis and trans conformation-specific antibodies1819, has a major effect on numerous phosphorylated proteins in cancer signaling pathways20. It has been shown that Pin1 is overexpressed and/or overactivated in the majority of human cancers including breast, lung, colon, prostate and liver cancers, with its levels being correlated with poor outcomes in cancer patients212223242526. In contrast, genetic single nucleotide polymorphism that reduces Pin1 expression is associated with reduced cancer risk for numerous cancers27.…”

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confidence: 99%

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

Yan

Zhu

et al. 2017

Sci Rep

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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.

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Section: Resultsmentioning

confidence: 74%

mentioning

confidence: 99%

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

Yan

Zhu

et al. 2017

Sci Rep

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“…Further work showed that stably expressing miR-200c induces anoikis in these cells by directly targeting TrkB, a neurotrophic tyrosine receptor kinase. Zhang and colleagues also studied the role of miR-200 in anoikis in breast cancer [78]. Transfection of miR-200b in MDA-MB-231, BT549, and Hs578T TNBC cells increased the number of apoptotic cells in suspension-culture.…”

Section: The Mir-200 Family In Cancer Metastasismentioning

confidence: 99%

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

2015

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MicroRNAs (miRNAs) are a large family of small non-coding RNAs that negatively regulate protein-coding gene expression post-transcriptionally via base pairing between the 5′ seed region of a miRNA and the 3′ untranslated region (3′UTR) of a messenger RNA (mRNA). Recent evidence has supported the critical role that miRNAs play in many diseases including cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429) is an emerging miRNA family that has been shown to play crucial roles in cancer initiation and metastasis, and potentially be important for the diagnosis and treatment of cancer. While miR-200s were found to be critically involved in the metastatic colonization to the lungs in mouse mammary xenograft tumor models, a large number of studies demonstrated their strong suppressive effects on cell transformation, cancer cell proliferation, migration, invasion, tumor growth and metastasis. This review aims to discuss research findings about the role of the miR-200 family in cancer initiation, each step of cancer metastatic cascade, cancer diagnosis and treatment. A comprehensive summary of currently validated miR-200 targets is also presented. It is concluded that miR-200 family may serve as novel targets for the therapy of multiple types of cancer.

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“…Currently, three miRNAs have been shown to negatively regulate PIN1 expression in cancers. miR-200b/c and miR-296-5p directly target and suppress PIN1 expression in breast cancer and prostate cancer cells, respectively[36-38]. However, no specific miRNA has been reported to target PIN1 expression in HCC.…”

Section: Regulation Of Pin1 Expression and Activitymentioning

confidence: 99%

Understanding the role of PIN1 in hepatocellular carcinoma

Cheng¹,

Leong²,

Tse³

2016

WJG

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PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation. PIN1 has been found to be over-expressed in many cancers, including human hepatocellular carcinoma (HCC). It has been shown previously that overexpression of PIN1 contributes to the development of HCC in-vitro and in xenograft mouse model. In this review, we first discussed the aberrant transcription factor expression, miRNAs dysregulation, PIN1 gene promoter polymorphisms and phosphorylation of PIN1 as potential mechanisms underlying PIN1 overexpression in cancers. Furthermore, we also examined the role of PIN1 in HCC tumourigenesis by reviewing the interactions between PIN1 and various cellular and viral proteins that are involved in β-catenin, NOTCH, and PI3K/Akt/mTOR pathways, apoptosis, angiogenesis and epithelial-mesenchymal transition. Finally, the potential of PIN1 inhibitors as an anti-cancer therapy was explored and discussed.

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Regulation of the MicroRNA 200b (miRNA-200b) by Transcriptional Regulators PEA3 and ELK-1 Protein Affects Expression of Pin1 Protein to Control Anoikis

Cited by 44 publications

References 59 publications

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

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

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

Understanding the role of PIN1 in hepatocellular carcinoma

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