circPAN3 exerts a profibrotic role via sponging miR-221 through FoxO3/ATG7-activated autophagy in a rat model of myocardial infarction

Li, Fēi; Long, Tianyi; Bi, Sisi; Sheikh, Sayed Ali; Chenglong, Zhang

doi:10.1016/j.lfs.2020.118015

Cited by 40 publications

(30 citation statements)

References 30 publications

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“…Previous studies have confirmed the role of mir221 in regulating autophagy (34,35). TGF-β1-induced HSc activation abnormally decreases autophagy (36), which seems to be consistent with the present results showing increased LC3II and P62 expression, indicating disruption of autophagy.…”

Section: Discussionsupporting

confidence: 93%

miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

Cheng

Yang

2021

Mol Med Rep

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liver fibrosis is a serious threat to human life and health. activated hepatic stellate cells (HScs) play a key role in the occurrence and development of liver fibrosis. Studies have reported that micrornas (mirnas/mirs) are involved in the pathological process of fibrosis, as well as its relevance in clinical diagnosis. However, the role of miR221 in hepatic fibrosis remains controversial. Remarkably, transforming growth factor-β (TGF-β1) caused HSc dysfunction in autophagic activation, characterized by an increase in P62 aggregation and lc3ii expression. The present study aimed to determine whether autophagy regulates hepatic fibrosis by mediating HSc activation and explore the potential targets leading to the sequence of events associated with miR221. The expression of miR221 was quantified in a liver fibrosis model in vivo and in vitro, and its specific target gene lysosome-associated membrane glycoprotein 2 (laMP2) was predicted by bioinformatics. The results showed that the expression levels of collagen-i (col-i) and α-smooth muscle actin (α-SMA) were increased in miR221-overexpressing LX2 cells, while the autophagy inducer rapamycin reversed the inhibition of autophagic flux induced by miR221. Additionally, the overexpression of laMP2 could significantly inhibit TGF-β1-induced col-i and α-SMA expression, which was similar to the effect of the mir221 inhibitor on the regulation of TGF-β1-induced HSc activation. These results indicated that mir221 may regulate TGF-β1-induced HSc activation through inhibiting autolysosome function by directly targeting laMP2. The molecular mechanism of mir221 in regulating TGF-β1-induced HSc activation may provide novel insight into therapies to ameliorate the pathological progression of liver fibrosis.

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Section: Discussionsupporting

confidence: 93%

miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

Cheng

Yang

2021

Mol Med Rep

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“…In another study of acute myeloid leukemia, circ-PAN3 was demonstrated to be a key mediator for chemo-resistance of AML cells through circ-PAN3-miR-153-5p/miR-183-5p-XIAP regulatory axis [17]. In cardiac brosis, circ-PAN3 exhibited pro brotic effects via miR-221/FoxO3/ATG7 axis [18]. However, the role and potential mechanisms of circ-PAN3 in HCC remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ-PAN3 (hsa_circ_0100181) Promotes Hepatocellular Carcinoma Growth Through Sponging miR-153 to Elevate Cyclin D1 Expression

Wang

et al. 2020

Preprint

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Background: Circular RNAs (circRNAs) are engaged in hepatocellular carcinoma (HCC) progression, but the mechanisms remain to be elucidated. This study aimed to unveil the expression pattern and potential biological mechanisms of a newly indentified circRNA, circ-PAN3, in HCC. Methods: Cell Counting Kit-8 (CCK‐8) assay and colony formation assay were used to assess cell proliferation. Transcription-quantitative PCR (RT-qPCR) analysis and western blot analysis were used to determine the relative expression level of mRNA and protein, respectively. Cell apoptosis assay was used to evaluate the apoptosis rate of transfected cells. CircInteractome and Targetscan were utilized to predict the possible targets of circRNAs and miRNAs, respectively. Luciferase reporter assay and RNA pull-down assay were used to assess the direct interaction of RNAs. HCC cancer xenograft model was used to evaluate the biological process of circ-PAN3 in vivo. Student’s t test, χ2 test or one-way ANOVA was adopted appropriately.Results: Circ-PAN3 was elevated in HCC tissues, and patients with high Circ-PAN3 expression had a poor survival outcome. Knockdown of circ-PAN3 expression suppressed cell viability, colony formation and cell proliferation in vitro and in vivo. Circ-PAN3 elevates cyclin D1 expression to promote HCC progression. Subsequently, using CircInteractome, miR-153 were confirmed to interact with circ-PAN3 and was downregulated by circ-PAN3. Further, using Targetscan, cyclin D1 was validated to interact with miR-153 and was downregulated by miR-153. Addition of miR-153 expression with corresponsive mimics significantly reduced the expression of cyclin D1. Notably, the inhibition of cell viability, colony formation and proliferation induced by knockdown of circ-PAN3 were recovered following the combination with miR-153 inhibitor, cyclin D1, respectively. Conclusion: Together, this study demonstrated that a novel circ-PAN3/miR-153/cyclin D1 axis regulatory axis that promoted HCC progression.

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“…circRNA_000203 can competitively bind to anti-fibrotic miR-26b-5p, enhancing the fibrotic phenotype in CFs ( 46 ). Similarly, circPAN3 exhibits pro-fibrotic effects via the miR-221/FoxO3/ATG7 axis ( 47 ). Another study showed that circHIPK3 is markedly upregulated in CFs and heart tissues treated with Ang-II ( 48 ).…”

Section: Circrna As Cerna In Cvdsmentioning

confidence: 99%

Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

Xue

Liu

Xiong

2021

Front. Cardiovasc. Med.

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Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

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circPAN3 exerts a profibrotic role via sponging miR-221 through FoxO3/ATG7-activated autophagy in a rat model of myocardial infarction

Cited by 40 publications

References 30 publications

miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

miR221 regulates TGF-β1-induced HSC activation through inhibiting autophagy by directly targeting LAMP2

Circular RNA circ-PAN3 (hsa_circ_0100181) Promotes Hepatocellular Carcinoma Growth Through Sponging miR-153 to Elevate Cyclin D1 Expression

Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

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