<i>MCM7</i>and its hosted miR-25, 93 and 106b cluster elicit YAP/TAZ oncogenic activity in lung cancer

Sardo, Federica Lo; Forcato, Mattia; Sacconi, Andrea; Capaci, Valeria; Zanconato, Francesca; Agostino, Silvia Di; Sal, Giannino Del; Pandolfi, Pier Paolo; Strano, Sabrina; Bicciato, Silvio; Blandino, Giovanni

doi:10.1093/carcin/bgw110

Cited by 52 publications

(43 citation statements)

References 49 publications

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“…Among the differentially expressed miRNAs in NASH-derived HCC, three miRNAs, miR-106b, miR-93, and miR-25, are members of the oncogenic miR-106b∼25 intragenic cluster [ 15 , 16 ]. This cluster is highly conserved in vertebrates and is located in the 13 th intron of the Mcm7 gene on mouse chromosome 5 (Figure 4A ) and human chromosome 7.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis

et al. 2017

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Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related death in the United States. Recent epidemiological studies have identified nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), as a major risk factor for HCC. Elucidating the underlying mechanisms associated with the development of NASH-derived HCC is critical for identifying early biomarkers for the progression of the disease and for treatment and prevention. In the present study, using liver samples from C57BL/6J mice submitted to the Stelic Animal Model (STAM) of NASH-associated liver carcinogenesis, we investigated the role of microRNA (miRNA) alterations in the pathogenesis of NASH-derived HCC. We found substantial alterations in the expression of miRNAs, with the greatest number occurring in full-fledged HCC. Mechanistically, altered miRNA expression was associated with activation of major hepatocarcinogenesis-related pathways, including the TGF-β, Wnt/β-catenin, ERK1/2, mTOR, and EGF signaling. In addition, the over-expression of the miR-221-3p and miR-222-3p and oncogenic miR-106b∼25 cluster was accompanied by the reduced protein levels of their targets, including E2F transcription factor 1 (E2F1), phosphatase and tensin homolog (PTEN), and cyclin-dependent kinase inhibitor 1 (CDKN1A). Importantly, miR-93-5p, miR-221-3p, and miR-222-3p were also significantly over-expressed in human HCC. These findings suggest that aberrant expression of miRNAs may have mechanistic significance in NASH-associated liver carcinogenesis and may serve as an indicator for the development of NASH-derived HCC.

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Section: Resultsmentioning

confidence: 99%

MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis

et al. 2017

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“…Previous studies on YAP have helped to elucidate EGFR‐TKI resistance in lung adenocarcinomas, showing that sustained YAP expression is essential for survival of TKI‐resistant cells 19,28 . Hippo pathway transcriptional coactivator YAP/TAZ and microRNA regulation have either a pro‐oncogenic or an elicit‐oncogenic role in different systems 28‐30 . The underlying mechanism of how statins increase the effectiveness of EGFR‐TKI for lung cancer cells inside the human body remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

et al. 2020

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Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population‐based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non‐statins and 41 statins users who had undergone EGFR‐TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan‐Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non‐statins group (4‐y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%‐81.4% vs. 85.5%; 95% CI, 78.5%‐98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29‐0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41‐0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR‐TKIs and played a synergistic anticancer role.

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“…Several oncogenic miRNA genes (e.g. those encoding miR-25, miR-93, and miR-106b) have been reported to be upregulated in NSCLCs [35]. However, hypomethylation was identified as mechanism for upregulation of only a few miRNA genes (e.g.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of microRNA‐coding genes in non‐small‐cell lung cancer patients

Heller

Altenberger

Steiner

et al. 2018

The Journal of Pathology

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Deregulated DNA methylation leading to transcriptional inactivation of certain genes occurs frequently in non‐small‐cell lung cancers (NSCLCs). As well as protein‐coding genes, microRNA (miRNA)‐coding genes may be targets for methylation in NSCLCs; however, the number of known methylated miRNA genes is still small. Thus, we investigated methylation of miRNA genes in primary tumour (TU) samples and corresponding non‐malignant lung tissue (NL) samples of 50 NSCLC patients by using methylated DNA immunoprecipitation followed by custom‐designed tiling microarray analyses (MeDIP‐chip), and 252 differentially methylated probes between TU samples and NL samples were identified. These probes were annotated, which resulted in the identification of 34 miRNA genes with increased methylation in TU samples. Some of these miRNA genes were already known to be methylated in NSCLCs (e.g. those encoding miR‐9‐3 and miR‐124), but methylation of the vast majority of them was previously unknown. We selected six miRNA genes (those encoding miR‐10b, miR‐1179, miR‐137, miR‐572, miR‐3150b, and miR‐129‐2) for gene‐specific methylation analyses in TU samples and corresponding NL samples of 104 NSCLC patients, and observed a statistically significant increase in methylation of these genes in TU samples (p < 0.0001). In silico target prediction of the six miRNAs identified several oncogenic/cell proliferation‐promoting factors (e.g. CCNE1 as an miR‐1179 target). To investigate whether miR‐1179 indeed targets CCNE1, we transfected miR‐1179 gene mimics into CCNE1‐expressing NSCLC cells, and observed downregulated CCNE1 mRNA expression in these cells as compared with control cells. Similar effects on cyclin E1 expression were seen in western blot analyses. In addition, we found a statistically significant reduction in the growth of NSCLC cells transfected with miR‐1179 mimics as compared with control cells. In conclusion, we identified many methylated miRNA genes in NSCLC patients, and found that the miR‐1179 gene is a potential tumour cell growth suppressor in NSCLCs. Overall, our findings emphasize the impact of miRNA gene methylation on the pathogenesis of NSCLCs. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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MCM7and its hosted miR-25, 93 and 106b cluster elicit YAP/TAZ oncogenic activity in lung cancer

Cited by 52 publications

References 49 publications

MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis

MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

DNA methylation of microRNA‐coding genes in non‐small‐cell lung cancer patients

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