Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets

Ramírez‐Salazar, Eric G.; Salinas-Silva, Luis Carlos; Vázquez-Manriquez, María Eugenia; Gayosso-Gómez, Luis Vicente; Negrete-García, María Cristina; Ramírez-Rodríguez, Sandra Lizbeth; Chávez, Raúl; Zenteno, Edgar; Santillán, Patricio; Kelly-García, Javier; Ortiz‐Quintero, Blanca

doi:10.1016/j.yexmp.2014.09.016

Cited by 30 publications

(25 citation statements)

References 60 publications

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“…Recently, numerous studies have revealed that miR-101-3p emerges as an essential modulator in the development of human cancers (Ramirez-Salazar et al, 2014;Floor et al, 2015). As an example, miR-101-3p could serve as a diagnostic biomarker of HCC .…”

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Chen

Zhang

2018

Cell Biology International

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Radioresistance is a major obstacle in hepatocellular carcinoma (HCC) radiotherapy. Aberrant expression of long non-coding RNA (lncRNA) has been postulated to be implicated in the development of HCC radioresistance. We investigated the role of lncRNA nuclear enriched abundant transcript 1_2 (NEAT1_2) in radioresistance of HCC and its molecular mechanism in this study. We found that NEAT1_2 and WEE1 were upregulated, and miR-101-3p was downregulated in HCC tissues, as well as HCC cell lines. Downregulation of WEE1 sensitized the radiosensitivity of HCC cells, as evidenced by decreased survival fractions of Huh7 and PLC5 cells and increased percentage of apoptotic cells. Also, knockdown of NEAT1_2 exerted a reinforcing effect on the radiosensitivity of HCC cells. In addition, WEE1 was confirmed as a direct target of miR-101-3p. Upregulation of miR-101-3p obviously decreased the mRNA and protein levels of WEE1 compared with that in the miR-NC group, while transfection of anta-miR-101-3p presented the opposite effects. In parallel, NEAT1_2 was identified to interact with miR-101-3p, and NEAT1_2 upregulated the expression of WEE1 in Huh7 cells through sponging miR-101-3p. Besides, the reinforcing effect of NEAT1_2 silencing could be attenuated by downregulation of miR-101-3p. To conclude, our results support the concept that downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR-101-3p/WEE1 axis.

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Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Chen

Zhang

2018

Cell Biology International

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“…A recent study in humans revealed potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura (Ramírez-Salazar et al 2014). This study examined micro-RNA expression in a small number of mesothelioma cases ( n = 5) compared to an equal number of cases with pleural fibrosis and chronic inflammation or atypical mesothelial hyperplasia.…”

Section: Hypotheses On the Mechanistic Events Related To Genotoxicitymentioning

confidence: 99%

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Kuempel

Jaurand

Møller

et al. 2016

Critical Reviews in Toxicology

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In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.

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“…S2). Two other studies in MM generating miR microarray profiles also suggest that miR‐18a is significantly upregulated in MM cell lines and MM tumor tissue compared to normal tissue (Amatya et al ., ; Ramirez‐Salazar et al ., ). Although none of these studies identified any key downstream targets of miR‐18a, they do support our idea that miR‐18a plays an important role in MM.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, miR-31 has high homology binding to the PIAS3 3 0 UTR and has been reported as an onco-miR in lung cancer and is associated with a poor prognosis in MM (Liu et al, 2010;Matsumoto et al, 2014), although this is controversial (Ivanov et al, 2010). These three miRs were chosen as our top candidate regulators of PIAS3 expression along with miR-18a, which has been reported to be upregulated in both MM cell lines and MM tumor samples compared to normal tissue (Amatya et al, 2016;Balatti et al, 2011;Ramirez-Salazar et al, 2014). The upregulation of these four miR candidates in MM cell lines was validated by RT-qPCR (shown in Table 2).…”

Section: Pias3 Expression Is Unaffected By Proteasome Inhibitionmentioning

confidence: 99%

Post‐transcriptional regulation of PIAS3 expression by miR‐18a in malignant mesothelioma

et al. 2018

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Protein inhibitor of activated STAT3 (PIAS3) is an endogenous suppressor of signal transducer and activator of transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper‐activated in various cancers. We previously reported that in malignant mesothelioma (MM), low PIAS3 expression is associated with increased STAT3 activation and correlates with poor patient survival, yet the regulatory mechanism(s) governing PIAS3 expression in MM remain unclear. Here, we demonstrate that PIAS3 protein expression does not correlate with its mRNA level in MM cell lines, indicating that PIAS3 expression is regulated at a post‐transcriptional level. Inhibition of proteasomal degradation with MG132 (10 μm) or bortezomib (1 μm), alone and in combination, did not increase PIAS3 protein levels; furthermore, inhibition of protein synthesis by cycloheximide treatment did not decrease PIAS3 levels within 48 h, suggesting that PIAS3 expression is not actively regulated at a post‐translational level. To determine whether miRNA (miRs) can translationally regulate PIAS3 expression, we combined miR microarray analysis with bioinformatic screening to identify candidate miRs, in MM cell lines with low PIAS3 expression, followed by luciferase reporter assays to validate miR regulation of the PIAS3 3′UTR. We identified miR‐18a as a suppressor of PIAS3 expression that is upregulated in MM cells and whose inhibition can increase PIAS3 expression and suppress STAT3 activity. Moreover, we showed that miR‐18a inhibition can decrease MM cell viability and that its expression is negatively correlated with MM patient survival. Taken together, these results suggest that targeting miR‐18a may have therapeutic benefit in MM.

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Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets

Cited by 30 publications

References 60 publications

Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Downregulation of lncRNA NEAT1_2 radiosensitizes hepatocellular carcinoma cells through regulation of miR‐101‐3p/WEE1 axis

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Post‐transcriptional regulation of PIAS3 expression by miR‐18a in malignant mesothelioma

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