Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma.

Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma.
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蛋白质分析揭示胆管癌中 RNA 之间潜在的 isomiR 相关串扰

DOI:
10.1016/j.csbj.2021.10.014
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发表时间:
2021
影响因子:
6
通讯作者:
Li X
Li X
中科院分区:
生物学2区
文献类型:
--
作者:
Guo L;Dou Y;Yang Y;Zhang S;Kang Y;Shen L;Tang L;Zhang Y;Li C;Wang J;Liang T;Li X

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蛋白质谱鉴定了用于筛选相关ncRNA的关键基因。miRNAs和isomiRs均参与编码-非编码RNA调控网络。IsomiR相关的ceRNA网络暗示了RNA之间的复杂相互作用。胆管癌(CCA)是由胆管细胞产生的肿瘤。尽管一些基因在肿瘤的病理过程中发挥着重要作用,但不同RNA之间的相互作用或串扰对于理解肿瘤发生的详细分子机制非常重要,特别是讨论isomiRs与其他RNA之间的串扰。为了研究CCA中的关键基因,本研究采用蛋白质表达谱的方法,对mRNA-ncRNA网络中的潜在关键mRNA和相关非编码RNA(ncRNA)进行了研究,主要包括miRNA/isomiRs和lncRNA。如果在蛋白质和mRNA水平上发现一致的表达模式,则首先获得去调控的mRNA,并根据调控关系筛选相关的miRNAs/isomiRs。来自给定miRNA基因座的不同isomiR也有助于小RNA和靶mRNA之间的相互作用,并且miRNA进一步用于调查相关lncRNA以扩展相互作用。因此,构建了几组RNA作为候选竞争性内源RNA(ceRNA)网络。最后,我们发现RAB 11 FIP 1:miR-101- 3 p:MIR 3142 HG可能是一个潜在的ceRNA网络,由于存在多种异构体,它们之间的相互作用可能更加复杂。与此同时,还检测到了与RAB 11 FIP 1和miR-194- 5 p相关的其它lncRNA(FBXL 19-AS 1、SNHG 1和PVT 1),这些lncRNA可能在编码-非编码RNA调控网络中起着关键作用。我们的研究结果表明,具有序列和表达异质性的不同isomiRs有助于ceRNA调控网络,可能在CCA中发挥关键作用,这将扩大我们对不同RNA之间的相互作用及其在癌症发展中的贡献的理解。
Protein profiling identified crucial genes that were used to screen related ncRNAs. Both miRNAs and isomiRs were involved in coding-non-coding RNA regulatory network. IsomiR-associated ceRNA networks implied the complex interactions among RNAs. Cholangiocarcinomas (CCAs) are tumors that arise from the cholangiocytes. Although some genes have been shown with important roles in pathological process, interactions or cross-talks among different RNAs are important to understand the detailed molecular mechanisms in cancer development, especially discussing cross-talks among isomiRs and other RNAs. Herein, to characterize crucial genes in CCA, the protein expression profile was performed to survey potential crucial mRNAs and related non-coding RNAs (ncRNAs) in mRNA-ncRNA network, mainly including miRNAs/isomiRs and lncRNAs. Deregulated mRNAs were firstly obtained if consistent expression patterns were found at protein and mRNA levels, and related miRNAs/isomiRs were screened according to regulatory relationships. Diverse isomiRs from a given miRNA locus also contributed to interactions between the small RNAs and target mRNAs, and miRNAs were further used to survey related lncRNAs to expand the interactions. Thus, several groups of RNAs were constructed as candidate competitive endogenous RNA (ceRNA) networks. Finally, we found that RAB11FIP1:miR-101-3p:MIR3142HG may be a potential ceRNA network, and the interactions among them may be more complex due to variety of isomiRs. Simultaneously, RAB11FIP1 and miR-194-5p were also detected other related lncRNAs (FBXL19-AS1, SNHG1 and PVT1) that may be crucial in coding-non-coding RNA regulatory network. Our results show that diverse isomiRs with sequence and expression heterogeneities contribute to ceRNA regulatory network that may have crucial roles in CCA, which will expand our understanding of interactions among diverse RNAs and their contributions in cancer development.
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