Dataset Information

Integrative multiplatform-based molecular profiling of human colorectal cancer reveals proteogenomic alterations underlying mitochondrial inactivation.

ABSTRACT: Mitochondria play leading roles in initiation and progression of colorectal cancer (CRC). Proteogenomic analyses of mitochondria of CRC tumor cells would likely enhance our understanding of CRC pathogenesis and reveal new independent prognostic factors and treatment targets. However, comprehensive investigations focused on mitochondria of CRC patients are lacking. Here, we investigated global profiles of structural variants, DNA methylation, chromatin accessibility, transcriptome, proteome, and phosphoproteome on human CRC. Proteomic investigations uncovered greatly diminished mitochondrial proteome size in CRC relative to that found in adjacent healthy tissues. Integrated with analysis of RNA-Seq datasets obtained from the public database containing mRNA data of 538 CRC patients, the proteomic analysis indicated that proteins encoded by 45.5% of identified prognostic CRC genes were located within mitochondria, highlighting the association between altered mitochondrial function and CRC. Subsequently, we compared structural variants, DNA methylation, and chromatin accessibility of differentially expressed genes and found that chromatin accessibility was an important factor underlying mitochondrial gene expression. Furthermore, phosphoproteomic profiling demonstrated decreased phosphorylation of most mitochondria-related kinases within CRC versus adjacent healthy tissues, while also highlighting MKK3/p38 as an essential mitochondrial regulatory pathway. Meanwhile, systems-based analyses revealed identities of key kinases, transcriptional factors, and their interconnections. This research uncovered a close relationship between mitochondrial dysfunction and poor CRC prognosis, improve our understanding of molecular mechanism underlying mitochondrial linked to human CRC, and facilitate identifies of clinically relevant CRC prognostic factors and drug targets.

SUBMITTER: Zhang W

PROVIDER: S-EPMC8263689 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundEpstein-Barr virus (EBV) is an important human pathogenic gammaherpesvirus with carcinogenic potential. The EBV transcriptome has previously been analyzed using both Illumina-based short read-sequencing and Pacific Biosciences RS II-based long-read sequencing technologies. Since the various sequencing methods have distinct strengths and limitations, the use of multiplatform approaches have proven to be valuable. The aim of this study is to provide a more complete picture on the transcriptomic architecture of EBV.MethodsIn this work, we apply the Oxford Nanopore Technologies MinION (long-read sequencing) platform for the generation of novel transcriptomic data, and integrate these with other's data generated by another LRS approach, Pacific BioSciences RSII sequencing and Illumina CAGE-Seq and Poly(A)-Seq approaches. Both amplified and non-amplified cDNA sequencings were applied for the generation of sequencing reads, including both oligo-d(T) and random oligonucleotide-primed reverse transcription. EBV transcripts are identified and annotated using the LoRTIA software suite developed in our laboratory.ResultsThis study detected novel genes embedded into longer host genes containing 5'-truncated in-frame open reading frames, which potentially encode N-terminally truncated proteins. We also detected a number of novel non-coding RNAs and transcript length isoforms encoded by the same genes but differing in their start and/or end sites. This study also reports the discovery of novel splice isoforms, many of which may represent altered coding potential, and of novel replication-origin-associated transcripts. Additionally, novel mono- and multigenic transcripts were identified. An intricate meshwork of transcriptional overlaps was revealed.ConclusionsAn integrative approach applying multi-technique sequencing technologies is suitable for reliable identification of complex transcriptomes because each techniques has different advantages and limitations, and the they can be used for the validation of the results obtained by a particular approach.

Dataset Information

Integrative multiplatform-based molecular profiling of human colorectal cancer reveals proteogenomic alterations underlying mitochondrial inactivation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets