Guo Li, Dou Yuyang, Yang Yifei, Zhang Shiqi, Kang Yihao, Shen Lulu, Tang Lihua, Zhang Yaodong, Li Changxian, Wang Jun, Liang Tingming, Li Xiangcheng
Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
Department of Biology, Brandeis University, Waltham, MA, USA.
Comput Struct Biotechnol J. 2021 Oct 14;19:5722-5734. doi: 10.1016/j.csbj.2021.10.014. eCollection 2021.
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.
胆管癌（CCAs）是起源于胆管上皮细胞的肿瘤。尽管一些基因已被证明在病理过程中发挥重要作用，但不同RNA之间的相互作用或串扰对于理解癌症发生发展的详细分子机制至关重要，尤其是探讨异源微小RNA（isomiRs）与其他RNA之间的串扰。在此，为了鉴定胆管癌中的关键基因，我们进行了蛋白质表达谱分析，以在mRNA-非编码RNA网络中探寻潜在的关键mRNA和相关非编码RNA（ncRNAs），主要包括微小RNA/异源微小RNA（miRNAs/isomiRs）和长链非编码RNA（lncRNAs）。如果在蛋白质和mRNA水平发现一致的表达模式，则首先获得失调的mRNA，并根据调控关系筛选相关的微小RNA/异源微小RNA（miRNAs/isomiRs）。来自给定微小RNA位点的多种异源微小RNA（isomiRs）也有助于小RNA与靶mRNA之间的相互作用，并且进一步利用微小RNA（miRNAs）探寻相关的长链非编码RNA（lncRNAs）以扩展相互作用。因此，构建了几组RNA作为候选竞争性内源性RNA（ceRNA）网络。最后，我们发现RAB11FIP1:miR-101-3p:MIR3142HG可能是一个潜在的ceRNA网络，并且由于多种异源微小RNA（isomiRs）的存在，它们之间的相互作用可能更为复杂。同时，还检测到RAB11FIP1和miR-194-5p与其他可能在编码-非编码RNA调控网络中起关键作用的相关长链非编码RNA（FBXL19-AS1、SNHG1和PVT1）。我们的结果表明，具有序列和表达异质性的多种异源微小RNA（isomiRs）有助于ceRNA调控网络，该网络可能在胆管癌中起关键作用，这将扩展我们对不同RNA之间相互作用及其在癌症发生发展中作用的理解。
