379,275 research outputs found

    The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing

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    Lin-41 is a stem cell-specific E3 ligase and a known target of the tumour suppressor microRNA (miRNA) let-7. Lin-41 was recently reported to mediate ubiquitylation and degradation of the miRNA pathway protein Ago2. We demonstrate that Lin-41 is over-expressed in hepatocellular carcinoma (HCC). Lin-41 over-expression correlates with high a-fetoprotein level, high tumour grade and high tumour stage and predicts early tumour recurrence. Lin-41 is a strong predictor of poor long-term survival for patients with HCC. Lin-41 knock-down by RNA interference in HCC cell lines Huh7 and Hep3B suppressed proliferation in vitro and reduced in vivo tumour growth in NOD/SCID mice. On the other hand, over-expression of Lin-41 in the HCC cell line SK-Hep1 enhanced tumourigenicity. Over-expression and knock-down of Lin-41 led to inverse changes in the levels of Ago1 and Ago2 proteins. Over-expression of Ago1 and Ago2 reduced in vivo tumour growth. Lin-41 over-expression suppressed let-7 activity in HCC cell lines and expression of Lin-41 enhanced the expression of let-7-regulated oncogenes c-Myc, Lin-28B, HMGA2 and type 1 insulin-like growth factor receptor (IGF1R). Expression of Lin-28B and c-Myc enhanced the expression of Lin-41. Chromatin immunoprecipitation and reporter assays revealed direct association of c-Myc with the Lin-41 promoter, resulting in transcriptional transactivation. Our results indicate that Lin-41 plays an important role in the growth of HCC by regulating RISC complex proteins Ago1 and Ago2 to inhibit miRNA-mediated gene silencing and promote the expression of oncogenic proteins. Lin-41 is also a strong prognostic factor for patients with HCC. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

    Fig 34 in A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan

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    Fig 34. Type locality and habitat of Nigidius wushuae sp. n.Published as part of Lin, J.-Z., 2022, A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan, pp. 19-28 in Far Eastern Entomologist 451 on page 27, DOI: 10.25221/fee.451.4, http://zenodo.org/record/716659

    Figs 1–5 in A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan

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    Figs 1–5. Nigidius wushuae sp. n. 1 – male holotype, habitus, dorsal view; 2 – the same,Published as part of Lin, J.-Z., 2022, A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan, pp. 19-28 in Far Eastern Entomologist 451 on page 21, DOI: 10.25221/fee.451.4, http://zenodo.org/record/716659

    Figs 6–9. Nigidius lohi, holotype. 6 in A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan

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    Figs 6–9. Nigidius lohi, holotype. 6 – habitus, dorsal view; 7 – the same, ventral view; 8 –Published as part of Lin, J.-Z., 2022, A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan, pp. 19-28 in Far Eastern Entomologist 451 on page 21, DOI: 10.25221/fee.451.4, http://zenodo.org/record/716659

    Figs 24–29 in A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan

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    Figs 24–29. Male (24–26) and female (27–29) genitalia of Nigidius spp. 24, 27 – N.Published as part of Lin, J.-Z., 2022, A new species of the genus Nigidius MacLeay (Coleoptera: Lucanidae) from the Green Island, Eastern Taiwan, pp. 19-28 in Far Eastern Entomologist 451 on page 24, DOI: 10.25221/fee.451.4, http://zenodo.org/record/716659
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