br Conclusion The promoter of OGDHL gene is hypermethylated
Conclusion: The promoter of OGDHL gene is hypermethylated in colorectal cancer and might be considered as a biomarker for its development.
Keywords: Colorectal cancer; Oxoglutarate dehydrogenase like; OGDHL; methylation; Epigenetic
Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of death in the world.1 Accumulation of genetic and especially epigenetic alterations in epithelial genome which deteriorate genome transductions are believed to mainly contribute to tumori-genesis and eventually initiation and progression of colorectal cancer.2 Aberrant methylation of CpG island harboring promoter regions is a major epigenetic process which mainly involves tu-mor suppressor genes and results in decreased gene expression.3 In transformation of normal epithelial cells as well as tumor tissue progression from initial to late stages and metastasis, DNA methylation along with other genetic defects frequently happens and plays major role, al-though it is not merely the cause of cancer, but attributes a deriver role in cancer develop-ment.4,5 As one of the most early molecular changes in tumorigenesis of colorectal cancer, de-tection of methylation aberrations would be of interesting approaches toward early diagnosis and management of CRC.6 Early interventions would indeed assuage early diagnosis and treat-ment as well as reducing cancer mortality.7
Oxoglutarate dehydrogenase like (OGDHL) is a subunit of oxoglutarate dehydrogenase (OGDH) complex, which degrades glucose and glutamate, and its gene is located on 10q11.23 compris-ing of 24 exons.8 Being located in the mitochondrial matrix, OGDHL is involved in tricarboxylic MIK665 (S-64315) cycle and responsible for induction of apoptosis where its roles as a tumor suppressor gene have been suggested in previous studies.9,10 Mitochondria and mainly oxoglutarate complex are the main source of reactive oxygen species inside the cell that is involved in c-Jun N-terminal kinase cascade and apoptosis initiation.11 It is assumed that reactive oxygen species blockage is a procarcinogenic pathway of PI3K/AKT/mTOR and NF-KB12 and thus reduced expression of OGDHL can be supposed to be of importance in transformation of epithelial cells. Previous stud-ies have reported hypermethylation of OGDHL promoter being involved in breast, cervix, lung, esophagus, pancreas, clone, ovary, kidney, and bladder cancers.11,13
Here, we evaluated the methylation status of OGDHL gene promoter in the tumor and tumor-free margin tissue samples of people with sporadic colorectal cancer, using quantitative methylation-specific PCR (qMSP) to reveal its potential as a biomarker for CRC development.
Methods and material
Study population and sample collection
In this case-control study, 40 CRC patients with same ethnicity and geographic residency were included and written informed consent was obtained from all participants concerning eth-ical protocols which were approved by the Ethical Committee of Tabriz University of Medical Sci-ences. All patients were precisely identified as CRC patients considering clinicopathologic find-ings and all were candidates for cancer surgery as a routine step in the treatment procedure, undergoing appropriate surgery at Imam Reza Hospital and Amiralmomenin Hospital, between 2016 and 2017. None of the patients were receiving preoperative chemotherapy and/or
Please cite this article as: M. Khalaj-kondori, M. Hosseinnejad and A. Hosseinzadeh et al., Aberrant hypermethyla-tion of OGDHL gene promoter in sporadic colorectal cancer, Current Problems in Cancer, https://doi.org/10.1016/j. currproblcancer.2019.03.001
ARTICLE IN PRESS
Primer sets for methylation analysis of OGDHL gene promoter using qMSP method.
Primer Sequences (5-3) Ta°C Product size (bp)