The oncogenic microRNA miR-21 promotes regulated necrosis in mice

Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Xiang, Hua; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Wang, Xiong; Wysoczynski, Marcin; Sithu, Srinivas D; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

doi:10.1038/ncomms8151

Cited by 80 publications

(81 citation statements)

References 46 publications

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“…Kuśnierz-Cabala B et al demonstrated that the expression levels of miR-126-5p, miR-148a-3p, miR-216a-5p, miR-551b-5p and miR-375 were significantly elevated in moderate and severe acute pancreatitis (SAP) when compared to control subjects; however, in mild acute pancreatitis (MAP) patients, only miR-216a-5p, miR-551b-5p, and miR-375 were highly expressed [13]. Ma X et al reported that miR-21 was overexpressed in a murine model of AP [14], and An F et al discovered that miR-24-3p, miR-361-5p, miR-1246 and miR-222-3p were constantly up-regulated, and miR-181a-5p was constantly down-regulated, in hypertriglyceridemia-induced acute pancreatitis patients [15]. Moreover, it has been reported that miR-375, miR-217, miR-148a, miR-216a, miR-122, miR-214 and miR-138 were increased in mesenteric lymph nodes from rats with AP, and miR-217, miR-375, miR-122 and miR-148a were also increased in matched rat plasma samples [16].…”

Section: Introductionmentioning

confidence: 99%

miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3

Liu¹,

Zou²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acute pancreatitis contributes to high mortality in pancreatitis patients, and miRNAs play a vital role in the development of acute pancreatitis (AP), however, its precise biological role remains largely elusive. Methods: To clarify the potential mechanisms of miRNAs in AP, we built mouse models of mild acute pancreatitis (MAP) and moderate/ severe acute pancreatitis (SAP). MiRNA microarray analysis and Real-time quantitative PCR (qRT-PCR) were used to analyze the expression of miRNA in MAP/SAP. TargetScan software, dual-luciferase gene reporter assays and Western blotting were used to assess the target genes of miR-155-5p in AP. Results: miR-155-5p was significantly decreased in MAP/SAP mice compared to controls. In pancreatic acinar AR42J cells transfected with miR-155-5p mimic, the expression of Rela and Traf3 notably decreased in both the caerulein- and TLC-S-induced groups compared with the negative control (NC); however, the expression of Rela and Traf3 notably increased after transfection with miR-155-5p inhibitor. Combined analysis using the TargetScan software and dual-luciferase gene reporter assays indicated that Rela and Traf3 were both targeted by miR-155-5p. Meanwhile, the expression of Ptgs2 also decreased after transfection of the AR42J cells with miR-155-5p mimic. The opposite results were found when miR-155-5p inhibitor was transfected into the AR42J cells. In addition, we treated caerulein- and TLC-S-induced AR42J cells with the Rela inhibitor helenalin and found that the expression of Rela, Traf3 and Ptgs2 decreased compared with the NC, while the expression of miR-155-5p did not show any significant difference. Furthermore, we found that miR-155-5p was significantly down-regulated in pancreatitis patients. Conclusion: miR-155-5p inversely regulated AP development through the Rela/Traf3/Ptgs2 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3

Liu¹,

Zou²,

Wang³

et al. 2018

Cell Physiol Biochem

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“…While apoptosis is considered to be rather immunosuppressive, necroptosis has been suggested to be proinflammatory and to initiate inflammation. Accordingly, studies implicated necroptosis in the pathogenesis of several inflammatory diseases, such as inflammatory bowel disease and kidney diseases (8,(12)(13)(14). Conversely, the role of programmed necrotic cell death in human inflammatory liver diseases still remains to be fully elucidated (15).…”

Section: Introductionmentioning

confidence: 99%

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Günther¹,

He²,

Kremer³

et al. 2016

Journal of Clinical Investigation

138

166

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“…High miR-21 levels are, therefore, considered to be a marker of immune cell activation (7). Regarding pathological necrosis, miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death receptor-mediated intrinsic apoptotic pathway (8).…”

Section: Introductionmentioning

confidence: 99%

Emerging role of microRNA-21 in cancer

2016

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Abstract. MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27 nucleotides in length that regulate gene expression at the post-translational level. miR-21 is one of the earliest identified cancer-promoting 'oncomiRs', targeting numerous tumor suppressor genes associated with proliferation, apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis have been extensively investigated. Recent studies have focused on the diagnostic and prognostic value of miR-21 as well as its implication in the drug resistance of human malignancies. The further use of miR-21 as a biomarker and target for cancer treatments is likely to improve the outcome for patients with cancer. The present review highlights recent findings associated with the importance of miR-21 in hematological and non-hematological malignancies. IntroductionMicroRNAs (miRs) are a class of naturally occurring short non-coding RNA molecules of 15-27 nucleotides in length that regulate eukaryotic gene expression at the post-transcriptional level. Almost 2,000 human miRNAs have been identified through cloning and/or sequence analysis (1). They have key regulatory roles in the development, differentiation and apoptosis of normal cells, as well as in the determination of the final phenotype of cancer cells, affecting carcinogenesis and metastatic potential (2). miR-21 is an abundantly expressed miRNA in mammalian cells, whose upregulation is associated with numerous types of cancer (3,4). By generation of a conditional miR-21 knock-in mouse, it was demonstrated that miR-21 functions as an oncogene with its overexpression resulting in malignant B-cell lymphoma (5). Indeed, miR-21 was found to be the only consistently upregulated miRNA in a study that profiled 540 clinical samples from cancer patients (6). The majority of studies on miR-21 have focused on its role in carcinogenesis and its clinical application. miR-21 is also expressed in hematopoietic cells of the immune system, including B/T cells, monocytes, macrophages and dendritic cells. High miR-21 levels are, therefore, considered to be a marker of immune cell activation (7). Regarding pathological necrosis, miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death receptor-mediated intrinsic apoptotic pathway (8). Biological function of miR-21The biological functions of various miRNAs, including miR-21, have been extensively investigated and miR-21 is

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The oncogenic microRNA miR-21 promotes regulated necrosis in mice

Cited by 80 publications

References 46 publications

miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3

miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Emerging role of microRNA-21 in cancer

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