miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines

Lin, Cliff Ji-Fan; Gong, Hong‐Yi; Tseng, Hung; Wang, Weilun; Wu, Jen‐Leih

doi:10.1016/j.bbrc.2008.07.154

Cited by 240 publications

(181 citation statements)

References 30 publications

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“…However, the stearic-acid-mediated decrease in GSIS was not completely reversed by miR-34a-5p inhibition, which implies that a non-miR-34a-5p-mediated mechanism operated in GSIS reduction. We also observed that miR-34a-5p levels were higher [40,41]. In our study, we confirmed that BCL-2 and BCL-W are direct targets of miR-34a-5p using luciferase activity assays.…”

Section: Discussionsupporting

confidence: 85%

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Hao

et al. 2016

Diabetologia

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Aims/hypothesis Serum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated. Methods Three groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively. The microRNA (miR) profiles of islets were determined by microarray screening. Islet injury was detected with co-staining using the TUNEL assay and insulin labelling. A lentiviral vector expressing anti-miRNA-34a-5p oligonucleotide (AMO-34a-5p) was injected into mice via an intraductal pancreatic route. Results In both mouse islets and cultured rat insulinoma INS-1 cells, stearic acid exhibited a stronger lipotoxic role than other fatty acids, owing to repression of B cell CLL/ lymphoma 2 (BCL-2) and BCL-2-like 2 (BCL-W) by stearic acid stimulation of miR-34a-5p. The stearic-acid-induced lipotoxicity and reduction in insulin secretion were alleviated by AMO-34a-5p. Further investigations in INS-1 cells revealed that p53 was involved in stearic-acid-induced elevation of miR-34a-5p, owing in part to activation of protein kinaselike endoplasmic reticulum kinase (PERK). Conversely, silencing PERK alleviated stearic-acid-induced p53, miR-34a-5p and lipotoxicity. Conclusions/interpretation These findings provide new insight for understanding the molecular mechanisms underlying not only the deleterious impact of stearic-acid-induced lipotoxicity but also apoptosis in beta cells and progression to type 2 diabetes.

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Section: Discussionsupporting

confidence: 85%

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Hao

et al. 2016

Diabetologia

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“…Overexpression of miR-122 in the HCC cell lines, HepG2 and HepG3, led to reduction of cell viability and activation of caspase-3. 49 Finally, Su et al found that miR-101 sensitized hepatoma cell lines to both serum-starvation-and chemotherapeutic-drug-induced apoptosis by repressing MCL-1, indicating that miR-101 may exert its proapoptotic function via targeting Mcl-1. 50 As described above, Mcl-1 is also a target of miR-29b, and is upregulated in cholangiocarcinoma cell lines that overexpress miR-29b.…”

Section: Gacgttcactgccac-ttg Gacgttcactgccac-ttg Gacgttcactgccac-ttg Mirmentioning

confidence: 99%

MicroRNAs as regulators of death receptors signaling

Garofalo¹,

Condorelli

Croce³

2009

Cell Death Differ

104

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Death receptors, belonging to the TNF receptor superfamily, induce apoptosis through two different pathways, one involving the effector caspases directly (type I cells or mitochondria-independent death), the other one amplifying the death signal through the mitochondrial pathway (type II cells or mitochondria-dependent death). MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the stability or translational efficiency of targeted messenger RNAs. MiRNAs are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. In this review we will discuss recent findings implicating miRNAs as regulators of death receptors and pro-and antiapoptotic genes involved in programmed cell death pathways.

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“…One of the most important mechanisms is represented by the inhibition of bcl-w, an antiapoptotic protein of bcl-2 family. High levels of mir-122 down-regulate bcl-w promoting apoptosis (Lin et al, 2008;Young et al, 2010;Xu et al, 2011b). Another important role was demonstrated by Fornari et al (2009).…”

Section: Mir-122mentioning

confidence: 94%

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Bronte

Fanale

et al. 2016

Critical Reviews in Oncology/Hematology

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miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines

Cited by 240 publications

References 30 publications

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway

MicroRNAs as regulators of death receptors signaling

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

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