Synonymous mutations that regulate translation speed might play a non-negligible role in liver cancer development

• Published in: BMC cancer Vol. 21; no. 1; p. 388
• Main Authors: Li, Qun, Li, Jian, Yu, Chun-Peng, Chang, Shuai, Xie, Ling-Ling, Wang, Song
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.04.2021; BioMed Central; BMC
• Subjects: Alleles; Biomarkers, Tumor; Cancer; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chromosome Mapping; Codon; Codon usage; Computational Biology - methods; COVID-19; Databases, Genetic; Development and progression; Disease; Disease Susceptibility; Gene expression; Gene mutations; Genes, Tumor Suppressor; Genetic aspects; Genetic translation; Genomes; Humans; Liver cancer; Liver Neoplasms - etiology; Liver Neoplasms - metabolism; Mutation; Oncogenes; Oncology, Experimental; Polymorphism, Single Nucleotide; Protein Biosynthesis; Severe acute respiratory syndrome coronavirus 2; Silent Mutation; Software; Structure; Synonymous mutations; Transcriptomes; Translation; Tumor suppressor genes; Tumors; Velocity; Web sites; China; Liver cancer; Synonymous mutations; Translation; Gene expression; Codon usage
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-08131-w

Synonymous mutations do not change the protein sequences. Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. We fully utilized the transcriptome and translatome of liver cancer and normal tissue from ten patients. We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. Synonymous mutations that increase the codon optimality significantly enhanced the translational velocity, and were enriched in oncogenes. Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. Synonymous mutations might play a role in liver cancer development by altering codon optimality and translational velocity. Synonymous mutations should no longer be ignored in the genome-wide studies.