MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Li, X; Zhang, J; Gao, Lin; McClellan, Steven; Finan, M.A.; Butler, T. W.; Owen, L B; Piazza, Gary A.; Xi, Yaguang

doi:10.1038/cdd.2011.127

Cited by 121 publications

(111 citation statements)

References 39 publications

(13 reference statements)

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“…However, we found that protein levels of SHP2 were not changed in HepG2 cells or the liver of mice when miR-181a was overexpressed (data not shown). RNA-binding protein LIN-28 homologue A, another target of miR-181a, has also been reported as a positive regulator of insulin signalling [46,47]. Foxo1 and Pgc1α were also predicted as miR-181a targets by PicTar or TargetScan.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

et al. 2012

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Aims/hypothesis Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. Methods Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. Results miR-181a targets the 3′ untranslated region (3′UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. Conclusions/interpretation miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

et al. 2012

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“…7 To date, about 1800 human miRNAs have been identified (miRBase Release 21.0, http://www.mirbase.org/), 8 including many that participate in key cellular processes, such as apoptosis, proliferation, and differentiation. 9 MiRNA misexpressions or mutations result in a gain or loss of miRNA function, resulting in the down-or up-regulation of the target protein. More importantly, the successful use of antagomirs to silence miRNAs in mice 10 and nonhuman primates 11 suggests the possible therapeutic use of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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Background: Lung cancer is the most common cancer that is caused by perturbation of regulatory pathways rather than dysfunction of a single gene. Cisplatin (CDDP; cis-diamminedichloroplatinum II) is the first member of a class of platinum-containing anti-cancer medication, which binds to DNA and triggers apoptosis. CDDP-based chemotherapy is used to treat various types of cancers. However, the efficacy of CDDP in the treatment of non-small-cell lung cancer (NSCLC) is limited by acquired drug resistance. MicroRNAs have recently emerged as key regulators of cancers, and miR-26a is one of downregulated miRNAs in A549/CDDP res cell line. This study aimed to investigate the role of miR-26a in CDDP resistance in NSCLC as well as the underlying mechanisms.Methods: In this study, we analyzed expressional profiles of CDDP resistance-related mRNA, miRNA, and transcription factors (TF) that regulate miRNA expression in NSCLC. A549 cells were treated with CDDP, miR-26a mimic, or miR-26a inhibitor, and followed by biological analysis including drug sensitivity assay, colony formation assay, terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay, and cell cycle analysis. Luciferase assay was used to determine the target of miR-26a. The regulation of miR-26a in Akt pathway was measured by western blot.Results: High mobility group A (HMGA) 2 was identified as the target of miR-26a. Overexpression of miR26a in A549 cells inhibited G1-S transition, increased cell death in response to CDDP treatment, and decreased the colony formation of A549 cells. MiR-26a significantly decreased the expression of E2F1, diminished Akt phosphorylation, and downregulated Bcl2 expression. Cell growth was suppressed by inhibiting HMGA2-mediated E2F1-Akt pathway.Conclusion: MiR-26a is responsible for A549 cell sensitivity in the treatment of CDDP through regulating HMGA2-mediated E2F1-Akt pathway.

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“…The mammalian genome encodes two homologues of the C. elegans lin-28 genes (LIN28A and LIN28B) (3,4), which may control gene expression by distinct molecular mechanisms (5). They are important in processes such as embryogenesis (6), skeletal myogenesis (7), germ cell development (8,9), neurogliogenesis (10,11), differentiation (12,13), lymphopoiesis (14), and glucose metabolism (15). Genome-wide association studies have implicated the LIN28B locus in controlling both height and the timing of menarche in humans (16 -20).…”

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confidence: 99%

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

Zhong

Lin

et al. 2012

Journal of Biological Chemistry

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Background: LIN28A may function as a critical oncogene in human cancer. Results: LIN28A controls expression of numerous cell cycle regulatory genes, including CDK2, CCND1, and CDC25A, in cancer. Conclusion: LIN28A promotes cell cycle progression in cancer mediated by both let-7-dependent and -independent mechanisms. Significance: Our data shed new light on how LIN28A regulates cell cycle in cancer.

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MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Cited by 121 publications

References 39 publications

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

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