Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

Wan, Jianhua; Yang, Xiaoyu; Ren, Yuping; Li, Xueyang; Zhu, Yin; Haddock, Ashley N.; Ji, Baoan; Xia, Liang; Lü, Nonghua

doi:10.1038/s41419-019-1545-x

Cited by 42 publications

(26 citation statements)

References 35 publications

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“…6A). Finally, it has been reported that inhibition of miR-155 improves prognosis in an experimental model of acute pancreatitis, making this miRNA a promising target for the design of therapeutical strategies for the treatment of pancreatitis 20 . Our results indicate that, in addition to the local synthesis, this miRNA could achieve the target macrophages via exosomes, providing a potential new point of control.…”

Section: Discussionmentioning

confidence: 99%

Acute pancreatitis promotes the generation of two different exosome populations

Jiménez-Alesanco

Marcuello

Pastor-Jiménez

et al. 2019

Sci Rep

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Exosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. However, proteomic analysis suggested that the most likely origin of these exosomes could be the liver instead of the pancreas. The present study aimed to characterize the exosomes released by pancreas to pancreatitis-associated ascitic fluid (PAAF) as well as those circulating in plasma in an experimental model of taurocholate-induced acute pancreatitis in rats. We provide evidence that during acute pancreatitis two different populations of exosomes are generated with relevant differences in cell distribution, protein and microRNA content as well as different implications in their physiological effects. During pancreatitis plasma exosomes, but not PAAF exosomes, are enriched in the inflammatory miR-155 and show low levels of miR-21 and miR-122. Mass spectrometry-based proteomic analysis showed that PAAF exosomes contains 10–30 fold higher loading of histones and ribosomal proteins compared to plasma exosomes. Finally, plasma exosomes have higher pro-inflammatory activity on macrophages than PAAF exosomes. These results confirm the generation of two different populations of exosomes during acute pancreatitis. Deep understanding of their specific functions will be necessary to use them as therapeutic targets at different stages of the disease.

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Section: Discussionmentioning

confidence: 99%

Acute pancreatitis promotes the generation of two different exosome populations

Jiménez-Alesanco

Marcuello

Pastor-Jiménez

et al. 2019

Sci Rep

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“…In 2019, Wan et al [ 114 ] established AP model by intraperitoneally injecting BALB/C mice with caerulein. Then investigating the effect of miR-155 in AP by injecting AAV-miR-155 and AAV-miR-155 sponge into the tail vein of mice.…”

Section: The Role Of Mirnas In Regulating Autophagy Of Apmentioning

confidence: 99%

Autophagy in Acute Pancreatitis: Organelle Interaction and microRNA Regulation

Yuan

Guo³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Acute pancreatitis (AP) is a common disorder with significant hospital admission and mortality. Due to the unclarified pathological mechanism, there is still no effective and specific treatment for AP. Recently, autophagy has been found to be closely related with occurrence and development of AP, which is crucial in determining its severity and outcomes. Emerging evidence indicates that autophagy can be regulated and influenced by microRNAs and organelles, including mitochondria, endoplasmic reticulum and lysosome, through various ways in AP. Of note, the complex interplays and close relationships among autophagy, microRNA and organelles in AP are vital for figuring out pathogenesis but not clear yet. Thus, this review summarizes the role of autophagy in the pathological mechanism of AP, especially the relationship between impaired autophagy and organelles, and discusses the regulatory mechanism of microRNA on autophagy, which could offer new insights into understanding the pathogenesis of AP and developing new potential therapeutic targets against AP.

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“…2b) 91,92 , a positive regulator of apoptosis, seems to play a pivotal role. Apart from hematologic malignancies, miR-155 is also overexpressed in several solid tumors, such as breast, colon, pancreatic, and lung cancer, and has also been described in the regulation of autophagy in an experimental mouse model of pancreatitis 93 . More recently, the therapeutic efficacy of an anti-miR-155 was tested in vivo by using a novel delivery system targeting the acidic tumor microenvironment: a nucleic acid anti-miR-155 linked to a peptide with a low pH-induced transmembrane structure (pHLIP) effectively inhibited miR-155 expression after intravenous administration, leading to cancer regression in a mouse model of lymphoma 94 .…”

Section: Mir-155mentioning

confidence: 99%

The role of noncoding RNAs in epithelial cancer

et al. 2020

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Regulatory noncoding RNAs (ncRNAs) are a class of RNAs transcribed by regions of the human genome that do not encode for proteins. The three main members of this class, named microRNA, long noncoding RNA, and circular RNA play a key role in the regulation of gene expression, eventually shaping critical cellular processes. Compelling experimental evidence shows that ncRNAs function either as tumor suppressors or oncogenes by participating in the regulation of one or several cancer hallmarks, including evading cell death, and their expression is frequently deregulated during cancer onset, progression, and dissemination. More recently, preclinical and clinical studies indicate that ncRNAs are potential biomarkers for monitoring cancer progression, relapse, and response to cancer therapy. Here, we will discuss the role of noncoding RNAs in regulating cancer cell death, focusing on those ncRNAs with a potential clinical relevance. Facts • Many of the genetic and epigenetics alterations in human cancers are found in noncoding regions of the DNA. How can we integrate preclinical findings to select the best regulatory ncRNA for clinical studies?

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Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

Cited by 42 publications

References 35 publications

Acute pancreatitis promotes the generation of two different exosome populations

Acute pancreatitis promotes the generation of two different exosome populations

Autophagy in Acute Pancreatitis: Organelle Interaction and microRNA Regulation

The role of noncoding RNAs in epithelial cancer

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