Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo.
Regeneration linked miRNA modify tumor phenotype and can enforce multi-lineage growth arrest in vivo.
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DOI：
10.1038/s41598-021-90009-9
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发表时间：
2021-05-18
影响因子：
4.6
通讯作者：
Aluvihare VR
中科院分区：
文献类型：
--
作者：
Salehi S;Tavabie OD;Villanueva A;Watson J;Darling D;Quaglia A;Farzaneh F;Aluvihare VR
调节的细胞增殖是再生的效应机制，而失调的细胞增殖是癌症的特征。我们以前已经确定了调节成功和失败的人类肝再生的microRNA（miRNA）。我们假设这些调节因子可能直接改变肿瘤的行为。在这里，我们表明，单独或组合抑制miRNA-503和-23 a在体外增强肝细胞和非肝细胞来源的癌症中的肿瘤增殖，从而在体内驱动更具侵袭性的肿瘤行为。抑制miRNA-152可诱导DNMT 1、位点特异性甲基化和相关的基因表达变化以及体外和体内生长抑制。在再生失败中观察到的两种miRNA表达的强制变化重演了体内多谱系癌症的完全生长抑制。我们的研究结果表明，再生和肿瘤侵袭性的调节是一致的，基于miRNA的再生抑制剂可能构成人类癌症的新治疗策略。
Regulated cell proliferation is an effector mechanism of regeneration, whilst dysregulated cell proliferation is a feature of cancer. We have previously identified microRNA (miRNA) that regulate successful and failed human liver regeneration. We hypothesized that these regulators may directly modify tumor behavior. Here we show that inhibition of miRNAs -503 and -23a, alone or in combination, enhances tumor proliferation in hepatocyte and non-hepatocyte derived cancers in vitro, driving more aggressive tumor behavior in vivo. Inhibition of miRNA-152 caused induction of DNMT1, site-specific methylation with associated changes in gene expression and in vitro and in vivo growth inhibition. Enforced changes in expression of two miRNA recapitulating changes observed in failed regeneration led to complete growth inhibition of multi-lineage cancers in vivo. Our results indicate that regulation of regeneration and tumor aggressiveness are concordant and that miRNA-based inhibitors of regeneration may constitute a novel treatment strategy for human cancers.
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影响因子：
3.9
作者：
Di Lonardo A;Nasi S;Pulciani S
通讯作者：
Pulciani S
DOI：
10.1126/science.1260825
发表时间：
2015-01-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tomasetti C;Vogelstein B
通讯作者：
Vogelstein B
影响因子：
13.5
作者：
Shu, Jingmin;Kren, Betsy T.;Xia, Zhilian;Wong, Phillip Y. -P.;Li, Lihua;Hanse, Eric A.;Min, Michael X.;Li, Bingshan;Albrecht, Jeffrey H.;Zeng, Yan;Subramanian, Subbaya;Steer, Clifford J.
通讯作者：
Steer, Clifford J.
影响因子：
8.8
作者：
Salehi, S.;Brereton, H. C.;Aluvihare, V. R.
通讯作者：
Aluvihare, V. R.
microRNA-148/152家族作为多种人类恶性肿瘤预后因素的重要性：荟萃分析
影响因子：
--
作者：
Miao, Chenkui;Zhang, Jianzhong;Wang, Zengjun
通讯作者：
Wang, Zengjun