Over‐expressed microRNA‐27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activation

Ji, Juling; Zhang, Jinsheng; Huang, Guangjian; Qian, Jin; Wang, Xueqing; Mei, Shuang

doi:10.1016/j.febslet.2009.01.034

Cited by 274 publications

(200 citation statements)

References 25 publications

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“…5 Emerging evidence has revealed that miRNAs are implicated in HSC activation and thereby regulate liver fibrosis. [6][7][8][9] For example, Wang et al reported that miR-29b prevents liver fibrosis by suppressing HSC activation and inducing cell apoptosis via targeting PI3K/ AKT pathway. 3 Our previous study found that curcumin upregulates miR-29b expression, leading to the silencing of DNA methyltransferase 3b (DNMT3b) and the loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) methylation, which contributes to suppression of activated HSCs.…”

Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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“…Thus, the percentage of cells in G 2 -M was consequently increased. Other studies also found that the suppression of miR-27a can inhibit gastric cancer cell growth [57] and overexpression of miR-27a increases the fat accumulation and cell proliferation of Hepatic stellate cells [58]. Therefore, miR-27a is considered as an oncogene.…”

Section: Discussionmentioning

confidence: 96%

A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk

Yang

Schlehe

Hemminki

et al. 2009

Breast Cancer Res Treat

113

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International audienceMicroRNAs (miRNAs) regulate pathways involved in cell differentiation, proliferation, development, and apoptosis by degradation of target mRNAs and/or repression of their translation. Although the single nucleotide polymorphisms (SNPs) in miRNAs target sites have been studied, the effects of SNPs in miRNAs are largely unknown. In our study, we first systematically sequenced miRNA genes reported to be involved in breast cancer to identify/verify SNPs. We analyzed four SNPs, one located in the pre-miRNA and the other three located in miRNA flanking regions, for a putative association with breast cancer risk. The SNP rs895819, located in the terminal loop of pre-miRNA-27a, showed a protective effect. In a large familial breast cancer study cohort, the rare [G] allele of rs895819 was found to be less frequent in the cases than in the controls, indicating a reduced familial breast cancer risk ([G] vs. [A]: OR = 0.88, 95% CI 0.78-0.99, = 0.0287). Furthermore, age stratification revealed that the protective effect was mainly observed in the age group < 50 years of age ([G] vs. [A]: OR = 0.83, 95% CI 0.70-0.98, = 0.0314), whereas no significant effect was observed in the age group ≥ 50 years of age, indicating a possible hormone-related effect. It has been shown that artificial mutations in the terminal loop of miR-27a can block the maturation process of the miRNA. We hypothesize that the G-variant of rs895819 might impair the maturation of the oncogenic miR-27a and thus, is associated with familial breast cancer risk

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“…However, we did not observe any effect of RBV treatment in OR6Ac cells (data not shown). The RXRα protein level is known to be regulated by microRNAs (miRNAs), such as miR‐27a40, 41 and miR‐34a,42 suggesting that these miRNAs may regulate RXRα expression in hepatic cells treated with RBV.…”

Section: Discussionmentioning

confidence: 99%

Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate‐activated protein kinase‐related kinases and retinoid X receptor α

Satoh

Mori

Onomura

et al. 2017

Hepatology Communications

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Ribavirin (RBV) has been widely used as an antiviral reagent, specifically for patients with chronic hepatitis C. We previously demonstrated that adenosine kinase, which monophosphorylates RBV into the metabolically active form, is a key determinant for RBV sensitivity against hepatitis C virus RNA replication. However, the precise mechanism of RBV action and whether RBV affects cellular metabolism remain unclear. Analysis of liver gene expression profiles obtained from patients with advanced chronic hepatitis C treated with the combination of pegylated interferon and RBV showed that the adenosine kinase expression level tends to be lower in patients who are overweight and significantly decreases with progression to advanced fibrosis stages. In our effort to investigate whether RBV affects cellular metabolism, we found that RBV treatment under clinically achievable concentrations suppressed lipogenesis in hepatic cells. In this process, guanosine triphosphate depletion through inosine monophosphate dehydrogenase inhibition by RBV and adenosine monophosphate‐activated protein kinase‐related kinases, especially microtubule affinity regulating kinase 4, were required. In addition, RBV treatment led to the down‐regulation of retinoid X receptor α (RXRα), a key nuclear receptor in various metabolic processes, including lipogenesis. Moreover, we found that guanosine triphosphate depletion in cells induced the down‐regulation of RXRα, which was mediated by microtubule affinity regulating kinase 4. Overexpression of RXRα attenuated the RBV action for suppression of lipogenic genes and intracellular neutral lipids, suggesting that down‐regulation of RXRα was required for the suppression of lipogenesis in RBV action. Conclusion: We provide novel insights about RBV action in lipogenesis and its mechanisms involving inosine monophosphate dehydrogenase inhibition, adenosine monophosphate‐activated protein kinase‐related kinases, and down‐regulation of RXRα. RBV may be a potential reagent for anticancer therapy against the active lipogenesis involved in hepatocarcinogenesis. (Hepatology Communications 2017;1:550–563)

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Over‐expressed microRNA‐27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activation

Cited by 274 publications

References 25 publications

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk

Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate‐activated protein kinase‐related kinases and retinoid X receptor α

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