Transcriptional machinery of TNF-α-inducible YTH domain containing 2 (YTHDC2) gene
- PMID: 24269672
- DOI: 10.1016/j.gene.2013.11.005
Transcriptional machinery of TNF-α-inducible YTH domain containing 2 (YTHDC2) gene
Abstract
We previously demonstrated that a cellular factor, cyclosporin A (CsA) associated helicase-like protein (CAHL) that is identical to YTH domain containing 2 (YTHDC2), forms trimer complex with cyclophilin B and NS5B of hepatitis C virus (HCV) and facilitates HCV genome replication. Gene expression of YTHDC2 was shown in tumor cell lines and tumor necrosis factor (TNF)-α-treated hepatocytes, but not in untreated. However, the function of YTHDC2 in the tumor cells and the mechanism by which the YTHDC2 gene is transcribed in these cells is largely unknown. We first evaluated that the role of YTHDC2 in the proliferation of hepatocellular carcinoma (HCC) cell line Huh7 using RNA interference and found that YTHDC2-downregulated Huh7 were significantly decreased cell growth as compared to control. We next demonstrated that the cAMP response element (CRE) site in the promoter region of the YTHDC2 gene is critical for YTHDC2 transcription. To further investigate the transcription factors bound to the CRE site, we performed chromatin immunoprecipitation assays. Our findings demonstrate that c-Jun and ATF-2 bind to the CRE site in Huh7, and that TNF-α induces the biological activity of these transcription factors in hepatocytes as well as Huh7. Moreover, treatment with the HDAC inhibitor, trichostatin A (TSA), reduces YTHDC2 expression in Huh7 and in TNF-α-stimulated hepatocytes. Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells.
Keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ATF-2; BAC; CAHL; CRE; Cell growth; ChIP; CsA; CyPB; DMSO; FBS; FLuc; G6PDH; HCC; HCV; HDAC; IKK; IL-1β; IL-6; IκB kinase; JNK; MTT; NF-κB; NS5B; PBS; PMA; RIP1; RNA helicase; RT-PCR; TNF receptor-associated death domain protein; TNF receptor-associated factor; TNF-α; TRADD; TRAF; TSA; YTH domain containing 2; YTHDC2; activating transcription factor 2; bZIP; bacterial artificial chromosome; basic leucine zipper; c-Jun; c-Jun N-terminal kinase; cAMP response element, HDAC, histone deacetylase; chromatin immunoprecipitation; cyclophilin B; cyclosporin A; cyclosporin A (CsA) associated helicase-like protein; dimethyl sulphoxide; fetal bovine serum; firefly luciferase; glucose-6-phosphate dehydrogenase; hepatitis C virus; hepatitis C virus NS5b protein; hepatocellular carcinoma; interleukin 1 β; interleukin 6; nuclear factor κB; phorbol myristate acetate; phosphate-buffered saline; receptor-interacting protein 1; reverse transcriptase-polymerase chain reaction; shRNA; short hairpin RNA; siRNA; small interfering RNA; trichostatin A; tumor necrosis.
Copyright © 2013 Elsevier B.V. All rights reserved.
Similar articles
-
Feedback regulation of telomerase reverse transcriptase: new insight into the evolving field of telomerase in cancer.Cell Signal. 2013 Dec;25(12):2462-8. doi: 10.1016/j.cellsig.2013.08.009. Epub 2013 Aug 29. Cell Signal. 2013. PMID: 23993966 Review.
-
Regulation of the MIR155 host gene in physiological and pathological processes.Gene. 2013 Dec 10;532(1):1-12. doi: 10.1016/j.gene.2012.12.009. Epub 2012 Dec 14. Gene. 2013. PMID: 23246696 Review.
-
C/EBPalpha is up-regulated in a subset of hepatocellular carcinomas and plays a role in cell growth and proliferation.Gastroenterology. 2010 Aug;139(2):632-43, 643.e1-4. doi: 10.1053/j.gastro.2010.03.051. Epub 2010 Mar 27. Gastroenterology. 2010. PMID: 20347819
-
Induction of high-molecular-weight (HMW) tumor necrosis factor(TNF) alpha by hepatitis C virus (HCV) non-structural protein 3 (NS3) in liver cells is AP-1 and NF-kappaB-dependent activation.Cell Signal. 2007 Feb;19(2):301-11. doi: 10.1016/j.cellsig.2006.07.002. Epub 2006 Aug 17. Cell Signal. 2007. PMID: 16916598
-
Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha signaling through effects on cellular IkappaB kinase.Mol Cell Biol. 2006 Apr;26(8):3048-59. doi: 10.1128/MCB.26.8.3048-3059.2006. Mol Cell Biol. 2006. PMID: 16581780 Free PMC article.
Cited by
-
The biological function of the N6-Methyladenosine reader YTHDC2 and its role in diseases.J Transl Med. 2024 May 24;22(1):490. doi: 10.1186/s12967-024-05293-6. J Transl Med. 2024. PMID: 38790013 Free PMC article. Review.
-
Construction and clinical evaluation of N6-methyladenosine risk signature of YTHDC2, IGF2BP2, and HNRNPC in head and neck squamous cell carcinoma.Hua Xi Kou Qiang Yi Xue Za Zhi. 2022 Dec 1;40(6):704-709. doi: 10.7518/hxkq.2022.06.012. Hua Xi Kou Qiang Yi Xue Za Zhi. 2022. PMID: 36416324 Free PMC article. Chinese, English.
-
YTHDC2 Promotes Malignant Phenotypes of Breast Cancer Cells.J Oncol. 2022 Oct 7;2022:9188920. doi: 10.1155/2022/9188920. eCollection 2022. J Oncol. 2022. PMID: 36245989 Free PMC article. Review.
-
The comprehensive expression and functional analysis of m6A modification "readers" in hepatocellular carcinoma.Aging (Albany NY). 2022 Aug 12;14(15):6269-6298. doi: 10.18632/aging.204217. Epub 2022 Aug 12. Aging (Albany NY). 2022. PMID: 35963644 Free PMC article.
-
Antisense transcription from lentiviral gene targeting linked to an integrated stress response in colorectal cancer cells.Mol Ther Nucleic Acids. 2022 May 18;28:877-891. doi: 10.1016/j.omtn.2022.05.029. eCollection 2022 Jun 14. Mol Ther Nucleic Acids. 2022. PMID: 35694213 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous