Li Genliang, Ni Anni, Tang Yulian, Li Shubo, Meng Lingzhang
Department of Biochemistry and Molecular Biology, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
PeerJ. 2020 Mar 20;8:e8680. doi: 10.7717/peerj.8680. eCollection 2020.
The tumor microenvironment (TM) in close contact with cancer cells is highly related to tumor growth and cancer metastasis. This study is to explore the biogenesis mechanism of a secondary hepatocellular carcinoma (HCC) based on the function of RNA binding proteins (RBPs)-encoding genes in the physiological microenvironment (PM).
The healthy and HCC mice were used to isolate the PM, pre-tumor microenvironment (PTM), and TM. The samples were analyzed using the technology of RNA-seq and bioinformatics. The differentially expressed RBPs-encoding genes (DERs) and differentially expressed DERs-associated genes (DEDs) were screened to undergo GO and KEGG analysis.
18 DERs and DEDs were identified in the PTM vs. PM, 87 in the TM vs. PTM, and 87 in the TM vs. PM. Those DERs and DEDs participated in the regulation of gene expression at the levels of chromatin conformation, gene activation and silencing, splicing and degradation of mRNA, biogenesis of piRNA and miRNA, ribosome assemble, and translation of proteins.
The genes encoding RBPs and the relevant genes are involved in the transformation from PM to PTM, then constructing the TM by regulating protein synthesis. This regulation included whole process of biological genetic information transmission from chromatin conformation to gene activation and silencing to mRNA splicing to ribosome assemble to translation of proteins and degradation of mRNA. The abnormality of those functions in the organic microenvironments promoted the metastasis of HCC and initiated the biogenesis of a secondary HCC in a PM when the PM encountered the invasion of cancer cells.
与癌细胞紧密接触的肿瘤微环境（TM）与肿瘤生长和癌症转移高度相关。本研究旨在基于生理微环境（PM）中RNA结合蛋白（RBP）编码基因的功能，探索继发性肝细胞癌（HCC）的发生机制。
使用健康小鼠和HCC小鼠分离PM、肿瘤前微环境（PTM）和TM。采用RNA测序技术和生物信息学对样本进行分析。筛选差异表达的RBP编码基因（DER）和差异表达的DER相关基因（DED），进行GO和KEGG分析。
在PTM与PM中鉴定出18个DER和DED，在TM与PTM中鉴定出87个，在TM与PM中鉴定出87个。这些DER和DED参与了染色质构象、基因激活与沉默、mRNA剪接与降解、piRNA和miRNA生物合成、核糖体组装以及蛋白质翻译等水平的基因表达调控。
编码RBP的基因及相关基因参与了从PM到PTM的转变，然后通过调节蛋白质合成构建TM。这种调节包括从染色质构象到基因激活与沉默、再到mRNA剪接、核糖体组装、蛋白质翻译以及mRNA降解的生物遗传信息传递的全过程。有机微环境中这些功能的异常促进了HCC的转移，并在PM遇到癌细胞侵袭时引发了继发性HCC的发生。
