RNA binding proteins involved in regulation of protein synthesis to initiate biogenesis of secondary tumor in hepatocellular carcinoma in mice.

Genliang Li,Yulian Tang,Anni Ni,Lingzhang Meng,Shubo Li

doi:10.7717/peerj.8680

Genliang Li, Yulian Tang + Show 3 more

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https://doi.org/10.7717/peerj.8680

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Abstract

BackgroundThe 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).MethodsThe 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.Results18 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.ConclusionThe 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.

Highlights

Malignant tumor, as a new ‘‘system’’ in the body, is gestated by the organic environment which is the time and space for a tumor system to survive and to proliferate, especially the microenvironment that is in close contact with cancer cells
The results showed that 18 differentially expressed RBPs-encoding genes (DERs) and DERs-associated genes (DEDs) were identified in the pre-tumor microenvironment (PTM)/physiological microenvironment (PM), 87 in tumor microenvironment (TM)/PTM, and 87 in the TM/PM
The results indicated that during the biogenesis of a secondary tumor in the mouse model of hepatocellular carcinoma (HCC), the healthy PM were firstly transformed into the PTM to meet cancer cells by expression upregulation of some DERs and DEDs, which blocked the normal physiological functions of mRNA, miRNA, and piRNA by binding those RNAs when it encountered the invasion of cancer cells

Summary

Introduction

As a new ‘‘system’’ in the body, is gestated by the organic environment which is the time and space for a tumor system to survive and to proliferate, especially the microenvironment that is in close contact with cancer cells. The genes encoding RBPs and the relevant genes are involved in the transformation from PM to PTM, 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

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Discussion

Conclusion