p53-dependent Induction of PVT1 and miR-1204

Barsotti, Anthony M.; Beckerman, Rachel; Laptenko, Oleg; Hüppi, Konrad; Caplen, Natasha J.; Prives, Carol

doi:10.1074/jbc.m111.322875

Cited by 168 publications

(180 citation statements)

References 53 publications

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“…Interestingly, miR‐1205 and let‐7i are positively regulated by p53,29, 30 and miR‐885‐5p and miR‐449b activate the p53 pathway 31, 32. Therefore, our results further strengthen the idea that the regulation of beta‐catenin by miRNAs is linked to p53 signaling 17.…”

Section: Discussionsupporting

confidence: 78%

MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β‐catenin and Wnt signaling

Indersie

Lesjean

Hooks

et al. 2017

Hepatology Communications

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Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant neoplasm, beta‐catenin protein accumulates and increases Wnt signaling due to recurrent activating mutations in the catenin‐beta 1 (CTNNB1) gene. Therefore, beta‐catenin is a key therapeutic target in HBL. However, controlling beta‐catenin production with therapeutic molecules has been challenging. New biological studies could provide alternative therapeutic solutions for the treatment of HBL, especially for advanced tumors and metastatic disease. In this study, we identified microRNAs (miRNAs) that target beta‐catenin and block HBL cell proliferation in vitro and tumor growth in vivo. Using our dual‐fluorescence‐FunREG system, we screened a library of 1,712 miRNA mimics and selected candidates inhibiting CTNNB1 expression through interaction with its untranslated regions. After validating the regulatory effect of nine miRNAs on beta‐catenin in HBL cells, we measured their expression in patient samples. Let‐7i‐3p, miR‐449b‐3p, miR‐624‐5p, and miR‐885‐5p were decreased in tumors compared to normal livers. Moreover, they inhibited HBL cell growth and Wnt signaling activity in vitro partly through beta‐catenin down‐regulation. Additionally, miR‐624‐5p induced cell senescence in vitro, blocked experimental HBL growth in vivo, and directly targeted the beta‐catenin 3′‐untranslated region. Conclusion: Our results shed light on how beta‐catenin‐regulating miRNAs control HBL progression through Wnt signaling inactivation. In particular, miR‐624‐5p may constitute a promising candidate for miRNA replacement therapy for HBL patients. (Hepatology Communications 2017;1:168‐183)

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Section: Discussionsupporting

confidence: 78%

MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β‐catenin and Wnt signaling

Indersie

Lesjean

Hooks

et al. 2017

Hepatology Communications

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“…Although the underlying mechanism is generally unknown, it has been proposed that the expression of certain lncRNAs in CRC can be initiated or modulated by genetic (eg, SNPs in BA318C17.1, 66 sequence mutation of MALAT-1 67 ), epigenetic (eg, MIR211-dependent regulation of LOC285194, histone deacetylationinduced hypoxia-mediated downregulation of lncRNA-LET/NPTN-IT1 68 ), and transcriptional (eg, TCF7L2-dependent regulation of CCAT2, 58 TP53-dependent regulation of PVT1 69 ) regulatory factors and may allow for the exact execution of malignant transformation to some extent. 58,67,68 Intriguingly, in addition to being affected by MIR211, 64 LOC285194 was also found to be regulated by genetic deletion (copy number variation) and TP53, 64,65 suggesting that the expression of specific lncRNAs may be regulated by several regulatory mechanisms.…”

Section: Regulation Of Lncrna Expressionmentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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“…6 These miRNAs have also been shown to play a role in controlling cell growth, apoptosis, senescence and autophagy in a p53-dependent fashion ( Table 1). [7][8][9][10][11][12][13][14][15][16][17][18][19][20] Recently, we identified miR-1246 as another novel p53 target miRNA. Interestingly, this miRNA regulates the expression of DYRK1A, a Down syndrome-associated kinase, 21 which inactivates a nuclear transcriptional factor called NFAT1C by phosphorylating it and preventing it from nuclear import.…”

Section: Mir-1246mentioning

confidence: 99%