MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer

Garofalo, Michela; Quintavalle, Cristina; Leva, Gianpiero Di; Zanca, Ciro; Romano, Giulia; Taccioli, Cristian; Liu, C G; Croce, Carlo M.; Condorelli, Gerolama

doi:10.1038/onc.2008.6

Cited by 263 publications

(197 citation statements)

References 37 publications

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“…We recently provided evidence that p27 Kip1 is involved in TRAIL resistance in non-small cell lung cancer (NSCLC). 22 We demonstrated that in TRAIL-resistant CALU-1 cells, miR-222 and miR-221 are overexpressed and target Gsk3-cFLIP pathway and TRAIL resistance C Quintavalle et al p27 Kip1 , inducing its downregulation. However, TRAILsensitive H460 cells exhibited reduced levels of miR-222 and miR-221 and increased p27 Kip1 expression.…”

Section: Resultsmentioning

confidence: 99%

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c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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Akt is a serine-threonine kinase that has an important role in transducing survival signals. Akt also regulates a number of proteins involved in the apoptotic process. To find new Akt interactors, we performed a two-hybrid screening in yeast using full-length Akt cDNA as bait and a human cDNA heart library as prey. Among 200 clones obtained, two of them were identified as coding for the c-FLIP L protein. c-FLIP L is an endogenous inhibitor of death receptor-induced apoptosis through the caspase-8 pathway. Using co-immunoprecipitation experiments of either transfected or endogenous proteins, we confirmed the interaction between Akt and c-FLIP L . Furthermore, we observed that c-FLIP L overexpression interferes with Gsk3-b phosphorylation levels. Moreover, through its effects on Gsk3b, c-FLIP L overexpression in cancer cells induced resistance to tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL). This effect was mediated by the regulation of p27 Kip1 and caspase-3 expression. These results indicate the existence of a new mechanism of resistance to TRAIL in cancer cells, and unexpected functions of c-FLIP L .

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Section: Resultsmentioning

confidence: 99%

“…21 In addition, we have recently shown that miRNAs regulate p27 Kip1 expression and TRAIL sensitivity. 22 Therefore, we addressed the question of whether the effect of c-FLIP L on TRAIL resistance was mediated through Gsk3b activity and thus on p27 expression levels.…”

Section: Resultsmentioning

confidence: 99%

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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“…This leads to deregulated expression of certain miRNAs [81], resulting in significant changes in their concentrations and compositions and, consequently, their activities (described as miRNA under-or overexpression), and these miRNAs are potential biomarkers of clinical relevance [82,83]. Previous studies have confirmed the usefulness of miRNAs as biomarkers of NSCLC [48,[84][85][86].…”

Section: Methods Of Mirna Expression Analysismentioning

confidence: 99%

“…In 2008, Garofalo et al [85] reported that NSCLC cells overexpressing miR-221/222 were TRAIL-resistant and showed an increase in migration and invasion capabilities. Later on, the same group [135] demonstrated that miR-34a and miR-34c, which are downregulated in NSCLC cell lines, could play a significant role in lung carcinogenesis by modulating the expression of PDGFR-α/β and thereby regulating TRAIL-induced cell death sensitivity.…”

Section: Mirnas As Modulators Of Trail-based Therapymentioning

confidence: 99%

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Florczuk¹,

Szpechcinski²,

Chorostowska‐Wynimko³

2017

Targ Oncol

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Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as nonsmall cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level.

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“…It is reported that when miR-221/222 was upregulated in NSCLC, TRAIL was resisted [19]. Two genes Kit and p27Kip1 are related to this kind of regulation and a study has revealed that a decrease in the level of p27Kip1 seems to explain a decreased sensitivity to TRAIL-related apoptosis [20].…”

Section: Oncogenesis Mirnas In Lung Cancermentioning

confidence: 99%

Effect of miRNAs in lung cancer suppression and oncogenesis

Zhang

Liu

2016

Open Life Sciences

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MicroRNA (miRNAs) is a group of small noncoding RNAs. It is involved in multiple cellular processes including proliferation, development, metabolism, differentiation and apoptosis; many of which are linked to several pathological conditions, including cancer. Lung cancer is one of the leading causes of mortality in the world: in 2008 for example, there were 163,000 deaths as a result of lung cancer. Despite technologies emerging which provide the potential for novel targeted therapies and improved early diagnoses, the overall rate of fiveyear survival still remains at only 15%. One reason for this disappointing statistic is related to the presentation of the disease, and specifically a lack of markers for early detection. Notably, the expression of some miRNAs has been reported to be involved in the diagnosis, classification and even prognosis of lung cancer. Tumorsuppressive and oncogenic miRNAs were found in lung carcinogenesis and the biological functions of these miRNAs have been validated in transplantable lung cancer models and human paired normal-malignant lung tissue banks. Some of these tumor-suppressive and oncogenic miRNAs related to lung cancer will be reviewed here. This article will focus on emphasing miRNAs effectiveness as a biomarker in lung carcinogenesis and candidate pharmacology. Furthermore, how these findings improve our understanding of lung cancer biology and therapy will also be discussed.

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MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer

Cited by 263 publications

References 37 publications

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Effect of miRNAs in lung cancer suppression and oncogenesis

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