کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1984104 | 1539921 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma
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کلمات کلیدی
POLR2AHepG2MTRGAPDHSAMBHMTSAHHcyRNA polymerase II - آرانای پلیمراز II HCC - HCCS-adenosylmethionine - اس-ادنوزیل متیونینBetaine - بتائینbetaine homocysteine methyltransferase - بتایین هوموسیستئین متیل ترانسفرازMat - ماتMethionine - متیونینmethionine adenosyltransferase - متیونین آدنوزیلت ترانسفرازMethionine synthase - متیونین سنتازhomocysteine - هوموسیستئینHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)Choline - کولینglyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma](/preview/png/1984104.png)
چکیده انگلیسی
The remethylation of homocyteine into methionine is catalyzed either by methionine synthase (MTR) or by betaine-homocysteine methyltransferase (BHMT), in the liver. Choline/betaine deficiency and impaired BHMT pathway have been associated with hepatocellular carcinogenesis, in animal models. The molecular mechanisms that impair the BHMT pathway are unknown. We aimed to investigate BHMT, BHMT2, and MTR expression in HepG2 cells and human hepatocarcinoma tissues. Transcripts were quantified by RT-qPCR and splicing was assessed by analysis of exon junctions and sequencing of variants. Protein expression was studied by Western Blot, immunohistochemistry and enzyme activity. Tumor tissue was compared with surrounding healthy tissue. RT-qPCR of HepG2 cells and of tumor samples showed a strong decrease of transcripts of BHMT and BHMT2, compared to normal. MTR transcript levels were not different. The decreased BHMT expression resulted from the transcription of a splicing variant that produced a frameshift in exon 4, with a premature termination codon in exon 5 and a loss of function of the gene. This splicing variant did not fit with any mechanism resulting from known splicing consensus sequences and was not detected in normal adult and fetal liver. Consistently, BHMT activity was abolished in HepG2 and protein expression was not detectable in HepG2 and in 5 of the 6 tumor samples, compared to normal tissues. In conclusion, a transcription variant of exon 4 produces a loss of function of BHMT in human hepatocarcinoma. Whether this abnormal transcription of BHMT is part or consequence of liver carcinogenesis should deserve further investigations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 2, February 2012, Pages 385-392
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 2, February 2012, Pages 385-392
نویسندگان
Hélène Pellanda, Farès Namour, Ma'atem Fofou-Caillierez, Aude Bressenot, Jean-Marc Alberto, Céline Chéry, Ahmet Ayav, Jean-Pierre Bronowicki, Jean-Louis Guéant, Thierry Forges,