Frequent promoter hypermethylation and down regulation of BNIP3: An early event during gallbladder cancer progression

Epigenetic alterations have been reported as one of the risk factors of gallbladder cancer. Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. Present study was ai...

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Veröffentlicht in:Digestive and liver disease 2022-09, Vol.54 (9), p.1257-1263
Hauptverfasser: Bharti, Amisha, Kar, Amrita Ghosh, Singh, Deepika, Ansari, Mumtaz Ahmad, Tewari, Mallika, Narayan, Gopeshwar, Singh, Sunita
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container_end_page 1263
container_issue 9
container_start_page 1257
container_title Digestive and liver disease
container_volume 54
creator Bharti, Amisha
Kar, Amrita Ghosh
Singh, Deepika
Ansari, Mumtaz Ahmad
Tewari, Mallika
Narayan, Gopeshwar
Singh, Sunita
description Epigenetic alterations have been reported as one of the risk factors of gallbladder cancer. Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. The expression analysis and methylation status of BNIP3 was performed by semi-quantitative reverse transcription polymerase chain reaction and Methylation-specific polymerase chain reaction respectively in 84 GBC patients and 29 gallstone tissues (used as normal controls). We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. Our results suggest that promoter hypermethylation is an early event and can be a frequent mechanism for downregulation of BNIP3 in GBC.
doi_str_mv 10.1016/j.dld.2022.01.121
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Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. The expression analysis and methylation status of BNIP3 was performed by semi-quantitative reverse transcription polymerase chain reaction and Methylation-specific polymerase chain reaction respectively in 84 GBC patients and 29 gallstone tissues (used as normal controls). We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. 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subjects DNA Methylation
Down-Regulation
Epigenetic alterations
Gallbladder Neoplasms
Humans
Membrane Proteins
Promoter hypermethylation
Promoter Regions, Genetic
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Tumor suppressor gene
title Frequent promoter hypermethylation and down regulation of BNIP3: An early event during gallbladder cancer progression
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