Comparative analysis of long noncoding RNAs in long-lived mammals provides insights into natural cancer-resistance
Comparative analysis of long noncoding RNAs in long-lived mammals provides insights into natural cancer-resistance
复制标题
对长寿哺乳动物中长链非编码 RNA 的比较分析提供了对天然抗癌性的见解
DOI：
10.1080/15476286.2020.1792116
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发表时间：
2020-07-18
期刊：
影响因子：
4.1
通讯作者：
Kong, Qing-Peng
中科院分区：
文献类型：
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作者：
Jiang, Jian-Jun;Kong, Qing-Peng
小鼠和大鼠是传统上用于肿瘤学研究的主要模式生物；然而，它们的寿命短，易患癌症，限制了它们在了解抗癌机制方面的应用。近年来，对裸鼹鼠（NMR）等非标准长寿哺乳动物的研究为天然抗癌机制提供了新的认识。长寿物种是如何在基因上保持长寿和抗癌的，这在很大程度上仍是一个谜。为了更好地了解长寿哺乳动物的潜在抗癌机制，我们广泛地鉴定了两种长寿哺乳动物——弓头鲸（BW, Balaena mysticetus）和布氏蝙蝠（BB, Myotis brandtii）的长链非编码RNA （lncRNA）转录本，并分析了它们的序列特征、表达模式及其与抗癌的相关性。与最长寿的啮齿动物裸鼹鼠（NMR, Heterocephalus glaber）相似，BW和BB lncrna在组织和生理阶段之间表现出较低的序列保守性和动态表达。通过k-mers聚类，发现75-136个BW、BB和NMR lncRNAs与人类衰老疾病相关的lncRNAs （Pearson’s r≥0.9,p < 0.01）密切相关。此外，我们观察到数千个BB和BW lncRNAs与潜在的肿瘤抑制因子强共表达（r >.8或r <-0.8, p < 0.01），表明lncRNAs可能参与长寿哺乳动物的抗癌调节。我们的研究为lncRNA在进化和抗癌方面的研究提供了基础。缩写：BW：弓头鲸；BB：勃兰特的球拍；核磁共振：裸鼹鼠；LLM：长寿哺乳动物；HTS：人类肿瘤抑制因子；PTS：潜在肿瘤抑制因子；与衰老有关的疾病；HAR-Lncs：与人类衰老疾病相关的lncrna；Kmer-lncs：通过k-mers聚类分析，长寿哺乳动物物种中与10个HAR-Lncs相关（Pearson 'sr≥0.9,p < 0.01）的lncRNAs；all -lncs：所有长寿哺乳动物的lncrna；SDE-lncs：显著差异表达的lncrna
ABSTRACT Mouse and rats are staple model organisms that have been traditionally used for oncological studies; however, their short lifespan and highly prone to cancers limit their utilizationsin understanding the mechanisms of cancer resistance. In recent years, several studies of the non-standard long-lived mammalian species like naked mole rat (NMR) have provided new insights of mechanisms in natural anti-cancer. How long-lived species genetically maintain longevity and cancer-resistance remains largely elusive. To better understand the underlying anti-cancer mechanisms in long-lived mammals, we genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals, bowhead whale (BW, Balaena mysticetus) and Brandt’s bat (BB, Myotis brandtii) and featured their sequence traits, expression patterns, and their correlations with cancer-resistance. Similar with naked mole rat (NMR, Heterocephalus glaber), the most long-lived rodent, BW and BB lncRNAs show low sequence conservation and dynamic expressions among tissues and physiological stages. By utilizing k-mers clustering, 75–136 of BW, BB and NMR lncRNAs were found in close relation (Pearson’s r ≥0.9, p < 0.01) with human ageing diseases related lncRNAs (HAR-Lncs). In addition, we observed thousands of BB and BW lncRNAs strongly co-expressed (r > 0.8 or r <-0.8, p < 0.01) with potential tumour suppressors, indicating that lncRNAs are potentially involved in anti-cancer regulation in long-lived mammals. Our study provides the basis for lncRNA researches in perspectives of evolution and anti-cancer studies. Abbreviations: BW: bowhead whale; BB: Brandt’s bat; NMR: naked mole rat; LLM: long-lived mammal; HTS: human tumour-suppressors; PTS: potential tumour suppressor; ARD: ageing related diseases; HAR-Lncs: lncRNAs that related with human ageing diseases; Kmer-lncs: lncRNAs in long-lived mammal species that corelated (Pearson’sr ≥0.9, p < 0.01) with the 10 HAR-Lncs by k-mers clustering; All-lncs: all the lncRNAs in long-lived mammal species; SDE-lncs: significant differentially expressed lncRNAs