MicroRNAs in Liver Regeneration

Chen, Xiaoyu; Zhao, Yingying; Wang, Fei; Bei, Yihua; Xiao, Junjie; Yang, Changqing

doi:10.1159/000430381

Cited by 40 publications

(30 citation statements)

References 105 publications

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“…To investigate the circRNA regulatory role in rat LR further, GO analysis was performed to annotate the biological functions of host linear transcripts during priming phase of rat LR, the result showed obviously that a significant amount of GO terms were related with the response to stress, energy metabolism and regulation of cell proliferation, which had been acknowledged as the important activities in the early stage of rat LR [1, 22, 31, 32]. The most enriched CC terms were about different kinds of plasma membranes.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration

Guo

Chen

et al. 2017

BMC Genomics

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BackgroundRat liver regeneration (LR) proceeds along a process of highly organized and ordered tissue growth in response to the loss or injury of liver tissue, during which many physiological processes may play important roles. The molecular mechanism of hepatocyte proliferation, energy metabolism and substance metabolism during rat LR had been elucidated. Further, the correlation of circular RNA (circRNA) abundance with proliferation has recently been clarified. However, the regulatory capacity of circRNA in rat LR remains a fascinating topic.ResultsTo investigate the regulatory mechanism of circRNA during priming phase of rat LR, high-throughput RNA sequencing technology was performed to unbiasedly profile the expression of circRNA during priming phase of rat LR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis was conducted to predict the functions of differentially expressed circRNAs and their host linear transcripts. Co-expression networks of circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed LR-related circRNAs and the condition of their miRNA binding sites. To excavate the key circRNAs in the early phase of rat LR, we comprehensively evaluated and integrated the relationship of expression level between the circRNAs and the linear transcripts as well as the distribution of miRNA binding sites in circRNA sequences.ConclusionsThis paper is the first to employ the comprehensive circRNA expression profile and to investigate circRNA-miRNA interactions during priming phase of rat LR. Two thousand four hundred twelve circRNAs were detected, and 159 circRNAs deriving from 116 host linear transcripts differentially expressed (p < 0.05). Six significantly changed circRNAs during priming phase of rat LR were screened as key circle molecules, and then were validated by qRT-PCR. This study will lay the foundation for revealing the functional roles of circRNAs during rat LR and help solve the remaining clinical problems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3476-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Cell proliferation was the most important physiological activity during rat LR [22]. Consequently, an intriguing possibility was raised that alternative circRNA formation might constitute a novel regulatory layer in rat LR.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration

Guo

Chen

et al. 2017

BMC Genomics

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“…MicroRNAs (miRNAs), non-coding short RNA molecules composed of 20-25 nucleotides, negatively regulate gene expression at the post-transcriptional level by binding to the 3’-UTR region of target mRNAs, thereby inhibiting translation or inducing mRNA degradation [5]. Prior studies have noted that miRNAs play a critical role in vascular diseases through regulating VSMCs and endothelial cell functions, such as proliferation, migration, apoptosis, and synthesis/secretion of ECM proteins [8-10].…”

Section: Introductionmentioning

confidence: 99%

MiR-29b Downregulation Induces Phenotypic Modulation of Vascular Smooth Muscle Cells: Implication for Intracranial Aneurysm Formation and Progression to Rupture

Zhao

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Our previous microarray results identified numerous microRNAs (miRNAs), including miR-29b, that were differentially expressed in the serum of intracranial aneurysm (IA) patients. The current study aimed to investigate whether miR-29b downregulation in IA could promote the phenotypic modulation of vascular smooth muscle cells (VSMCs) involved in the pathogenesis of aneurysm by activating ATG14-mediated autophagy. Methods: First, the levels of miR-29b and autophagy related genes (ATGs) between IA patients and normal subjects were compared. Next, we modified the level of miR-29b via lentivirus particles in the VSMCs and examined the effects of miR-29b on proliferation, migration, and phenotypic modulation of VSMCs from a contractile phenotype to a synthetic phenotype, as well as the levels of autophagy. Finally, the binding of miR-29b to the 3’UTR of ATG14 mRNA and its effects on ATG14 expression were analysed by a luciferase reporter assay and Western blot, respectively. Results: The level of miR-29b was decreased, and autophagy markers were increased in the IA patients compared to that of the normal subjects. Knockdown of miR-29b significantly promoted VSMCs proliferation and migration and, more importantly, induced the phenotypic modulation associated with autophagy activation, whereas miR-29b overexpression showed the opposite effects. The luciferase reporter assay demonstrated that ATG14 was a functional target gene of miR-29b. Notably, knockdown of ATG14 by siRNA apparently abrogated miR-29b inhibition-mediated phenotypic modulation. Conclusion: Downregulation of miR-29b induced VSMCs phenotypic modulation by directly activating ATG14-mediated autophagy, which is associated with the formation, growth and rupture of IAs.

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“…Some reports estimate that about 50% of human protein-coding genes are subject of miRNA regulation (Huntzinger and Izaurralde, 2011). Consistently, several studies have reported the involvement of miRNAs in hepatic differentiation of stem cells, liver development, and liver regeneration (Davoodian et al, 2014a;Chen et al, 2015;Mahgoub and Steer, 2016). Consistently, several studies have reported the involvement of miRNAs in hepatic differentiation of stem cells, liver development, and liver regeneration (Davoodian et al, 2014a;Chen et al, 2015;Mahgoub and Steer, 2016).…”

Section: Introductionmentioning

confidence: 71%

“…Notably, several miRNAs have been recently reported to be involved in hepatic differentiation of stem cells suggesting their critical role in differentiation induction (Cui et al, 2013;Davoodian et al, 2014b;Jung et al, 2016). Several studies have highlighted the importance of miR-122 involvement in liver proliferation, regeneration, and development Kim et al, 2011;Doddapaneni et al, 2013;Davoodian et al, 2014a;Chen et al, 2015;Raut and Khanna, 2016). Several studies have highlighted the importance of miR-122 involvement in liver proliferation, regeneration, and development Kim et al, 2011;Doddapaneni et al, 2013;Davoodian et al, 2014a;Chen et al, 2015;Raut and Khanna, 2016).…”

Section: Discussionmentioning

confidence: 99%

The combination of miR‐122 overexpression and Let‐7f silencing induces hepatic differentiation of adipose tissue‐derived stem cells

Davoodian

Lotfi

Soleimani

et al. 2017

Cell Biology International

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Human adipose tissue-derived stem cells (hADSCs) have been considered as a promising source for cell therapy of liver diseases due to their accessibility, abundance, and expression of hepatocyte markers. Currently, the important role of certain microRNAs (miRNAs) has been reported during hepatic differentiation of stem cells. However, the combination effect of miRNAs on hepatic differentiation of these cells needs to be more investigated. The present study seeks to determine whether the combination of miRNAs can enhance hepatic differentiation of hADSCs in the absence of any other stimulation. First, lentiviral transduction was used to overexpress miR-122 and silence let-7f in hADSCs for up to 21 days. Then, hepatic functionality was evaluated by analyzing specific hepatocyte genes and biochemical markers at different time points of differentiation induction. Stable miR-122 overexpression and let-7f silencing together in hADSCs resulted in increased expression of hepatocyte markers including ALB, AFP, CK18, CK19, and HNF4a. In addition, urea and albumin production, immunocytochemistry, and glycogen staining confirmed that the treated cells differentiated toward hepatocyte-like cells. Therefore, our findings demonstrate the possibility of using microRNAs to induce hADSCs into functional hepatocyte-like cells.

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MicroRNAs in Liver Regeneration

Cited by 40 publications

References 105 publications

Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration

Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration

MiR-29b Downregulation Induces Phenotypic Modulation of Vascular Smooth Muscle Cells: Implication for Intracranial Aneurysm Formation and Progression to Rupture

The combination of miR‐122 overexpression and Let‐7f silencing induces hepatic differentiation of adipose tissue‐derived stem cells

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