title: [Downregulation of OGDHL expression is associated with promoter hypermethylation in colorectal cancer].
abstract: Cell metabolic reprogramming is one of the cancer hallmarks. Glycolysis activation, along with suppression of oxidative phosphorylation and, to a lower extent, the TCA cycle, occurs in the majority of malignant tumors. A bioinformatics search for the glucose metabolism genes that are differentially expressed in colorectal cancer (CC) was performed using the data of The Cancer Genome Atlas (TCGA) Project. OGDHL for an oxoglutarate dehydrogenase complex subunit, which is involved in the TCA cycle and is indirectly responsible for the induction of apoptosis, was identified as one of the most promising candidates. A quantitative PCR analysis showed, on average, an eightfold downregulation of OGDHL in 50% (15/30) of CC samples. Based on the TCGA data, promoter hypermethylation was assumed to be a major mechanism of OGDHL inactivation. Bisulfite sequencing identified the OGDHL promoter region (+327 ... +767 relative to the transcription start site) that is often methylated in CC samples with downregulated ODGHL expression (80%, 8/10) and is possibly crucial for gene inactivation. Thus, frequent and significant OGDHL downregulation due to hypermethylation of a specific promoter region was demonstrated for CC. The OGDHL promoter methylation pattern was assumed to provide a marker for differential diagnosis of CIMP+ (CpG island methylator phenotype) tumors, which display dense hypermethylation of the promoter region in many genes.
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: M S
authors: MS
authors: Fedorova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.|Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: A V
authors: AV
authors: Kudryavtseva
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: V A
authors: VA
authors: Lakunina
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: A V
authors: AV
authors: Snezhkina
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: N N
authors: NN
authors: Volchenko
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: E N
authors: EN
authors: Slavnova
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: T V
authors: TV
authors: Danilova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.|Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: A F
authors: AF
authors: Sadritdinova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: N V
authors: NV
authors: Melnikova
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: A A
authors: AA
authors: Belova
authors: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia.
authors: K M
authors: KM
authors: Klimina
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: D V
authors: DV
authors: Sidorov
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: B Ya
authors: BY
authors: Alekseev
authors: Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: A D
authors: AD
authors: Kaprin
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.|Herzen Moscow Cancer Research Institute, Ministry of Health of the Russian Federation, Moscow, 125284 Russia.
authors: A A
authors: AA
authors: Dmitriev
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.|Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119121 Russia.
authors: G S
authors: GS
authors: Krasnov
keywords: DNA hypermethylation; OGDHL; bisulfite sequencing; colorectal cancer; expression downregulation; quantitative PCR