Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer

Kanaan, Ziad; Shesh, N.; Eichenberger, M. Robert; Barnes, Christopher; Dworkin, Amy M.; Weller, Clayton; Cohen, Eric; Roberts, Henry L.; Keskey, Bobby; Petras, Robert E.; Crawford, Nigel P.S.; Galandiuk, Susan

doi:10.1002/humu.22021

Cited by 108 publications

(54 citation statements)

References 39 publications

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“…MiR-181a also promoted tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1 [38]. In contrast, the expression levels of miR-181a were shown to increase during the progression from non-neoplasia to dysplasia in inflammatory bowel disease-associated CRC, whereas decrease when dysplasia develops into cancer [39]. Our study appears to support a tumor suppressor role for miR-181a-5p, in terms of cell proliferation and chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

et al. 2017

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BackgroundWith more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC.MethodsWe examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells.ResultsIn this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/β-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/β-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p.ConclusionsOur study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/β-catenin signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0583-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

et al. 2017

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“…Let-7e was down-regulated in colorectal cancer, non-small-cell lung carcinoma, esophageal cancer, lymphoma and ovarian cancer and functioned as a tumor suppressor [35–39]. In contrast, an increased let-7e expression was observed in retinoblastoma and synovial sarcoma [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair

Xiao

Cai

et al. 2017

J Ovarian Res

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BackgroundResistance to platinum-based chemotherapy remains a great challenge for ovarian cancer treatment. The human let-7 family contains 13 members located on nine different chromosomes, and most members have been implicated in the modulation of drug sensitivity in cancers. Our previous study showed that deregulation of let-7e in epithelial ovarian cancer (EOC) promoted the development of resistance to cisplatin. In the present study, we aimed to investigate the underlying mechanism and further evaluate the clinical value of let-7e in predicting chemo-response and prognosis in EOC.ResultsIn situ hybridization assays revealed a significantly decreased expression of let-7e in chemo-resistant EOC tissues compared with chemo-sensitive cases. Transfection with let-7e agomir sensitized EOC cells to cisplatin, down-regulated BRCA1 and Rad51 expression, and repressed the repair of cisplatin-induced DNA double strand break, while let-7e inhibitor exerted the opposite effects. In human EOC tissues, BRCA1 and Rad51 levels were increased in the chemo-resistant group compared with the sensitive group and were negatively correlated with let-7e. Low let-7e and high Rad51 were significantly associated with poor progression-free survival and overall survival and multivariate regression analyses showed that let-7e was an independent predictor for overall survival and chemotherapy response in EOC. Receiver operating characteristic analysis indicated that let-7e level was highly predictive of resistance to platinum-taxane chemotherapy with an area under the curve of 0.826.ConclusionsIn EOC, low let-7e leads to activation of BRCA1 and Rad51 expression and subsequent enhancement of DSB repair, which in turn results in cisplatin-resistance. Let-7e is a potential predictor for survival and chemo-response in EOC and re-expression of let-7e might be an effective strategy for overcoming chemo-resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-017-0321-8) contains supplementary material, which is available to authorized users.

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“…miR-146b shows increased abundance in the transition from normal tissue to dysplasia, but decreased abundance as dysplasia progresses to CAC ( 43 ). This suggests miR-146b is competently induced by activated STAT3 in early lesions, but becomes dysregulated during cancer progression.…”

Section: Discussionmentioning

confidence: 99%

STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-κB to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes

et al. 2014

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Interleukin-6 (IL-6)-mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a pathway the loss of which is associated with persistent STAT3 activation in human cancer. We found that the gene encoding the tumor suppressor microRNA miR-146b is a direct STAT3 target gene and its expression was increased in normal breast epithelial cells but decreased in tumor cells. Methylation of the miR-146b promoter, which inhibited STAT3-mediated induction of expression, was increased in primary breast cancers. Moreover, we found that miR-146b inhibited nuclear factor κB (NF-κB)-dependent production of IL-6, subsequent STAT3 activation, and IL-6/STAT3-driven migration and invasion in breast cancer cells, thereby establishing a negative feedback loop. In addition, higher expression of miR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation. Our results identify an epigenetic mechanism of crosstalk between STAT3 and NF-κB relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis.

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Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer

Cited by 108 publications

References 39 publications

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair

STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-κB to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes

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