PMID- 30280947 OWN - NLM STAT- MEDLINE DCOM- 20190626 LR - 20190626 IS - 1563-5279 (Electronic) IS - 0020-7454 (Linking) VI - 129 IP - 3 DP - 2019 Mar TI - Site specific hypermethylation of CpGs in Connexin genes 30, 26 and 43 in different grades of glioma and attenuated levels of their mRNAs. PG - 273-282 LID - 10.1080/00207454.2018.1526802 [doi] AB - AIM: Gliomas, the intracranial tumours are considered the deadliest malignancies. The gap junctional Connexins (Cxs) that maintain cellular homeostasis perform a unique function in glial tumour suppression. However, the differential methylation patterns of Cxs were not revealed in glioma so far. The current study attempts to categorise promoter methylation of Cx30 and Cx26 and intron methylation of Cx43 in different grades of human glioma. MATERIALS AND METHODS: About 85 glioma patients with pathologically confirmed grades and 15 control brain tissues were recruited in the study. Bisulphite-PCR-Single Stranded Conformation analysis(SSCA), Bisulphite sequencing and MeDIP-qPCR were carried out to assess methylation status and Cx mRNA levels were also analysed to evaluate the effect of methylation. RESULTS: We found that promoter CpG islands(CpGs) reside in Sp1 and Ap2 sites of Cx30 and 26 were hypermethylated in high grades (HG) of glioma rather than low grades. The input % of both was significantly increased (p < 0.03) in progressive grades. Interestingly, Cx43 could exhibit a significant increase (p < 0.05) in input % only in grade IV. While, Cx30 and 26 mRNAs were downregulated according to their methylation status in progressive fashion with grades, Cx43 was downregulated irrespective of intron methylation. CONCLUSION: Thus, we suggest that the sites and extent of methylation of Cxs (30 and 26 but not in 43) are found to be altered. In different grades of glioma can provide better appreciation of the grade of the patient and might help in strategies based on epigenetic approaches. FAU - J, Jayalakshmi AU - J J AD - a Department of Biochemistry , University of Madras , Chennai , Tamilnadu , India. FAU - Vanisree, Arambakkam Janardhanam AU - Vanisree AJ AD - a Department of Biochemistry , University of Madras , Chennai , Tamilnadu , India. FAU - Ravisankar, Shantha AU - Ravisankar S AD - b Department of Neuropathology , Tamilnadu Multispeciality Hospital , Chennai , Tamilnadu , India. FAU - K, Rama AU - K R AD - c Department of Neuropathology , Madras Medical College and Government General hospital , Chennai , Tamilnadu , India. LA - eng PT - Journal Article DEP - 20181023 PL - England TA - Int J Neurosci JT - The International journal of neuroscience JID - 0270707 RN - 0 (Connexin 30) RN - 0 (Connexin 43) RN - 0 (GJA1 protein, human) RN - 0 (RNA, Messenger) RN - 127120-53-0 (Connexin 26) SB - IM MH - Brain Neoplasms/genetics/*metabolism MH - Connexin 26/genetics/*metabolism MH - Connexin 30/genetics/*metabolism MH - Connexin 43/genetics/*metabolism MH - *CpG Islands/genetics MH - *DNA Methylation/genetics MH - Down-Regulation MH - Glioma/genetics/*metabolism MH - Humans MH - Introns MH - Neoplasm Grading MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics/*metabolism OTO - NOTNLM OT - Bisulphite sequencing OT - Connexin OT - CpG Island OT - MeDIP OT - methylation EDAT- 2018/10/04 06:00 MHDA- 2019/06/27 06:00 CRDT- 2018/10/04 06:00 PHST- 2018/10/04 06:00 [pubmed] PHST- 2019/06/27 06:00 [medline] PHST- 2018/10/04 06:00 [entrez] AID - 10.1080/00207454.2018.1526802 [doi] PST - ppublish SO - Int J Neurosci. 2019 Mar;129(3):273-282. doi: 10.1080/00207454.2018.1526802. Epub 2018 Oct 23.