title: Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.
abstract: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC.
  
  
  
  Using CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types.
  
  
  
  We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasiya Vladimirovna
authors.initials: AV
authors.lastname: Snezhkina
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.|National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: George Sergeevich
authors.initials: GS
authors.lastname: Krasnov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Andrew Rostislavovich
authors.initials: AR
authors.lastname: Zaretsky
authors.affiliation: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University Eastern Campus, Baltimore, Maryland, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Zhavoronkov
authors.affiliation: National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Kirill Mikhailovich
authors.initials: KM
authors.lastname: Nyushko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.|Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
authors.forename: Alexey Alexandrovich
authors.initials: AA
authors.lastname: Moskalev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Irina Yurievna
authors.initials: IY
authors.lastname: Karpova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasiya Isaevna
authors.initials: AI
authors.lastname: Afremova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasiya Valerievna
authors.initials: AV
authors.lastname: Lipatova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Dmitriy Vladimitovich
authors.initials: DV
authors.lastname: Kochetkov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Maria Sergeena
authors.initials: MS
authors.lastname: Fedorova
authors.affiliation: National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Nadezhda Nikolaevna
authors.initials: NN
authors.lastname: Volchenko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.|National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Asiya Fayazovna
authors.initials: AF
authors.lastname: Sadritdinova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Nataliya Vladimirovna
authors.initials: NV
authors.lastname: Melnikova
authors.affiliation: National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Dmitry Vladimirovich
authors.initials: DV
authors.lastname: Sidorov
authors.affiliation: State Hospital №57, Moscow, Russia.
authors.forename: Anatoly Yurievich
authors.initials: AY
authors.lastname: Popov
authors.affiliation: A.V. Vishnevsky Institute of Surgery, Moscow, Russia.
authors.forename: Dmitry Valerievich
authors.initials: DV
authors.lastname: Kalinin
authors.affiliation: National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Andrey Dmitrievich
authors.initials: AD
authors.lastname: Kaprin
authors.affiliation: National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: Boris Yakovlevich
authors.initials: BY
authors.lastname: Alekseev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexey Alexandrovich
authors.initials: AA
authors.lastname: Dmitriev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. rhizamoeba@mail.ru.|National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia. rhizamoeba@mail.ru.
authors.forename: Anna Viktorovna
authors.initials: AV
authors.lastname: Kudryavtseva
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009928:Organ Specificity / Q000235:genetics; D059368:RNA Isoforms; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D059368:RNA Isoforms
keywords: Adenocarcinoma; Alternative splicing; Colorectal cancer; Energy metabolism; Tumor-specific alternative mRNA transcripts