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Status |
Public on Aug 09, 2023 |
Title |
Hepatitis B virus X protein contributes to hepatocellular carcinoma via upregulation of KIAA1429 methyltransferase and mRNA m6A hypermethylation of HSPG2/Perlecan [MeRIP-Seq] |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx) mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Our findings indicate a potential interaction between KIAA1429 and HSPG2, thus could be novel targets in combating HBx-driven HCC and warrants further investigation.
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Overall design |
To decipher the underlying mechanisms by which HBx exerted tumour promoting effects in HCC, we carried out MeRIP sequencing to display the m6A epitranscriptomic changes in Huh7 cells that stably express HBx.
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Contributor(s) |
Sivasudhan E, Zhou J, Ma J, Liu S, Lu Z, Meng J, Blake N, Rong R |
Citation missing |
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Submission date |
Aug 09, 2023 |
Last update date |
Aug 09, 2023 |
Contact name |
Enakshi Sivasudhan |
Organization name |
Xi'an Jiaotong Liverpool University
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Street address |
111, Ren'ai Road, Suzhou Industrial Park
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City |
Suzhou |
ZIP/Postal code |
215123 |
Country |
China |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (4)
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GSM7698145 |
Huh7-HBx cells without Doxycycline treatment, Input control |
GSM7698146 |
Huh7-HBx cells without Doxycycline treatment, m6A enriched |
GSM7698147 |
Huh7-HBx cells with Doxycycline treatment, Input control |
GSM7698148 |
Huh7-HBx cells with Doxycycline treatment, m6A enriched |
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This SubSeries is part of SuperSeries: |
GSE240451 |
Hepatitis B virus X protein contributes to hepatocellular carcinoma via upregulation of KIAA1429 methyltransferase and mRNA m6A hypermethylation of HSPG2/Perlecan |
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Relations |
BioProject |
PRJNA1003825 |