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Omics evidence: single nucleotide variants transmissions on chromosome 20 in liver cancer cell lines
Quanhui Wang1, Bo Wen, Tong Wang
1Beijing Institute of Genomics, Chinese Academy of Sciences , No. 1 Beichen West Road, Beijing 100101, China.
Abstract:
Cancer genomics unveils many cancer-related mutations, including some chromosome 20 (Chr.20) genes. The mutated messages have been found in the corresponding mRNAs; however, whether they could be translated to proteins still requires more evidence. Herein, we proposed a transomics strategy to profile the expression status of human Chr.20 genes (555 in Ensembl v72). The data of transcriptome and translatome (the mRNAs bound with ribosome, translating mRNAs) revealed that ∼80% of the coding genes on Chr.20 were detected with mRNA signals in three liver cancer cell lines, whereas of the proteome identified, only ∼45% of the Chr.20 coding genes were detected. The high amount of overlapping of identified genes in mRNA and RNC-mRNA (ribosome nascent-chain complex-bound mRNAs, translating mRNAs) and the consistent distribution of the abundance averages of mRNA and RNC-mRNA along the Chr.20 subregions in three liver cancer cell lines indicate that the mRNA information is efficiently transmitted from transcriptional to translational stage, qualitatively and quantitatively. Of the 457 genes identified in mRNAs and RNC-mRNA, 136 were found to contain SNVs with 213 sites, and >40% of these SNVs existed only in metastatic cell lines, suggesting them as the metastasis-related SNVs. Proteomics analysis showed that 16 genes with 20 SNV sites were detected with reliable MS/MS signals, and some SNVs were further validated by the MRM approach. With the integration of the omics data at the three expression phases, therefore, we are able to achieve the overall view of the gene expression of Chr.20, which is constructive in understanding the potential trend of encoding genes in a cell line and exploration of a new type of markers related to cancers.
Insights
This study used a transomics approach to analyze chromosome 20 (Chr.20) gene expression in liver cancer. Findings reveal efficient mRNA to protein translation, identifying potential metastasis-related single nucleotide variants (SNVs).
Area of Science:
- Genomics
- Proteomics
- Cancer Biology
Background:
- Cancer genomics identifies numerous mutations, including in chromosome 20 (Chr.20) genes, with mRNA evidence but limited protein-level validation.
- Understanding the translation of mutated Chr.20 gene messages into proteins is crucial for cancer research.
Purpose of the Study:
- To profile the expression status of human Chr.20 genes using a transomics strategy.
- To investigate the efficiency of mRNA to protein translation for Chr.20 genes in liver cancer cell lines.
- To identify potential metastasis-related single nucleotide variants (SNVs) on Chr.20.
Main Methods:
- Employed a transomics strategy integrating transcriptome and translatome data.
- Analyzed ribosome nascent-chain complex-bound mRNAs (RNC-mRNA) to assess translating mRNAs.
- Utilized proteomics and targeted mass spectrometry (MRM) for protein-level validation of SNVs.
Main Results:
- Approximately 80% of Chr.20 coding genes showed mRNA signals, while only 45% were detected at the proteome level.
- Efficient transmission of gene information from transcriptional to translational stages was observed.
- Over 40% of identified SNVs on Chr.20 genes were exclusive to metastatic cell lines, suggesting a role in metastasis.
- 20 SNV sites in 16 Chr.20 genes were validated through proteomics and MRM.
Conclusions:
- The transomics approach provides a comprehensive view of Chr.20 gene expression across transcriptional, translational, and proteomic levels.
- Findings highlight the efficient translation of Chr.20 mRNA and identify potential metastasis-related SNVs.
- This integrated omics data is valuable for understanding gene expression trends and discovering novel cancer markers.
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