Comprehensive Analysis of Differentially Expressed Profiles of mRNA N6-Methyladenosine in Colorectal Cancer.

Na Li, Qin Guo, Qiao Zhang, Bai-Jun Chen, Xiao-An Li, Yan Zhou
Author Information
  1. Na Li: Department Of Gastroenterology, The First People's Hospital of Aksu District, Aksu, China.
  2. Qin Guo: The First Affiliated Hospital of Chengdu Medical College, School of clinical medicine, Chengdu Medical College, Chengdu, China.
  3. Qiao Zhang: The First Affiliated Hospital of Chengdu Medical College, School of clinical medicine, Chengdu Medical College, Chengdu, China.
  4. Bai-Jun Chen: The First Affiliated Hospital of Chengdu Medical College, School of clinical medicine, Chengdu Medical College, Chengdu, China.
  5. Xiao-An Li: Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
  6. Yan Zhou: Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.

Abstract

To comprehensively profile the landscape of the mRNA N-methyladenosine (mA) modification in human colorectal cancer (CRC). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was explored to compare the difference in mRNA N-methyladenosine (mA) methylation between CRC tissues and adjacent normal control (NC) tissue. RNA-sequencing (RNA-seq) was performed to transcribe differentially expressed mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq data was conducted to predict RNA-binding proteins (RBPs). MeRIP-seq identified 1110 differentially mA methylated sites (DMMSs) and 980 differentially mA methylated genes (DMMGs) in CRC, with 50.13% of all modified genes showing unique mA-modified peaks in CRC. RNA-seq showed 915 upregulated genes and 1463 downregulated genes in CRC. QRT-PCR verified the RNA-seq results by detecting the expression of some mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq identified 400 differentially mA methylated and expressed genes (DEGs), and pathway analysis detected that DMMGs and DEGs were closely related to cancer. After analyzing these DMMGs and DEGs through the GEPIA database, we found that the expression of B3GNT6, DKC1, SRPK1, and RIMKLB were associated with prognosis, and the expression of B3GNT6 and RIMKLB were associated with clinical stage. 17 RBPs were identified based on the DMMGs and DEGs, among which FXR1, FXR2, FMR1, IGF2BP2, IGF2BP3, and SRSF1 were obviously highly expressed in CRC, and FMR1, IGF2BP2, and IGF2BP3 were closely related to methylation, and might be involved in the development of CRC. This study comprehensively profiled mA modification of mRNAs in CRC, which revealed possible mechanisms of mA-mediated gene expression regulation.

Keywords

References

  1. Cancer Genet. 2016 Mar;209(3):70-4 [PMID: 26778106]
  2. Am J Cancer Res. 2021 Apr 15;11(4):1428-1445 [PMID: 33948366]
  3. Nat Rev Genet. 2015 Feb;16(2):98-112 [PMID: 25534324]
  4. Mol Cell. 2017 Sep 21;67(6):1059-1067.e4 [PMID: 28867294]
  5. Front Oncol. 2019 May 03;9:332 [PMID: 31131257]
  6. Int J Oncol. 2018 Feb;52(2):621-629 [PMID: 29345285]
  7. Biochemistry. 1975 Oct 7;14(20):4367-74 [PMID: 169893]
  8. Cell Struct Funct. 2019;44(1):29-39 [PMID: 30787206]
  9. Nat Neurosci. 2018 Feb;21(2):195-206 [PMID: 29335608]
  10. Annu Rev Genomics Hum Genet. 2014;15:127-50 [PMID: 24898039]
  11. Tumour Biol. 2016 Feb;37(2):2683-90 [PMID: 26404134]
  12. Nat Rev Mol Cell Biol. 2014 May;15(5):313-26 [PMID: 24713629]
  13. Open Med (Wars). 2019 Mar 02;14:25-31 [PMID: 30886897]
  14. Nucleic Acids Res. 2015 Jul 27;43(13):6557-67 [PMID: 26068471]
  15. Onco Targets Ther. 2019 Dec 31;12:11609-11621 [PMID: 32021241]
  16. J Biol Chem. 1990 Nov 25;265(33):20117-22 [PMID: 2173695]
  17. Biochem J. 2009 Jan 1;417(1):15-27 [PMID: 19061484]
  18. Biochem Biophys Res Commun. 2020 Jan 8;521(2):499-506 [PMID: 31677788]
  19. Cancer Res. 2011 Apr 1;71(7):2417-22 [PMID: 21447745]
  20. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3469-74 [PMID: 25733852]
  21. Can J Biochem. 1979 Jun;57(6):927-31 [PMID: 476526]
  22. J Cell Biochem. 2019 Jun;120(6):9810-9819 [PMID: 30525244]
  23. Cell Mol Gastroenterol Hepatol. 2021;12(2):633-651 [PMID: 33848642]
  24. J Biol Chem. 2019 Dec 27;294(52):19889-19895 [PMID: 31753916]
  25. Cell Res. 2018 May;28(5):507-517 [PMID: 29686311]
  26. Int J Clin Exp Pathol. 2017 Aug 01;10(8):8968-8973 [PMID: 31966766]
  27. Sci Rep. 2016 Apr 13;6:24345 [PMID: 27072590]
  28. EMBO J. 2020 Oct 15;39(20):e104514 [PMID: 32964498]
  29. Biochem Biophys Res Commun. 2015 Apr 3;459(2):201-207 [PMID: 25725156]
  30. Mol Cancer Res. 2014 Sep;12(9):1195-204 [PMID: 24807918]
  31. Cell Cycle. 2016 Jul 17;15(14):1874-82 [PMID: 27229378]
  32. Cell. 2013 Nov 7;155(4):793-806 [PMID: 24209618]
  33. Cell. 2015 Nov 5;163(4):999-1010 [PMID: 26593424]
  34. Nucleic Acids Res. 1979 Jun 25;6(8):2879-99 [PMID: 223130]
  35. Nucleic Acids Res. 1994 Feb 11;22(3):419-26 [PMID: 8127679]
  36. Nucleic Acids Res. 2013 Jan;41(Database issue):D262-7 [PMID: 23118484]
  37. J Gene Med. 2020 Nov;22(11):e3250 [PMID: 32639657]
  38. Mol Cell. 2007 Jul 6;27(1):3-16 [PMID: 17612486]
  39. Mol Cancer. 2020 Apr 3;19(1):72 [PMID: 32245489]
  40. J Exp Clin Cancer Res. 2020 Sep 29;39(1):203 [PMID: 32993738]
  41. Trends Genet. 2016 Jun;32(6):320-321 [PMID: 27050931]
  42. Cell Res. 2019 Jan;29(1):23-41 [PMID: 30514900]
  43. Nature. 2012 Apr 29;485(7397):201-6 [PMID: 22575960]
  44. Mol Cancer. 2019 Dec 4;18(1):176 [PMID: 31801551]
  45. Mol Cell. 2017 Dec 7;68(5):993-1005.e9 [PMID: 29107537]
  46. J Clin Lab Anal. 2020 Jan;34(1):e23026 [PMID: 31536166]
  47. F1000Res. 2020 Feb 11;9: [PMID: 32089836]
  48. J Clin Lab Anal. 2021 Sep;35(9):e23931 [PMID: 34398984]
  49. Oncol Lett. 2016 Jul;12(1):488-494 [PMID: 27347170]
  50. Cell Stem Cell. 2018 Feb 1;22(2):191-205.e9 [PMID: 29290617]
  51. Nucleic Acids Res. 2020 Apr 17;48(7):3816-3831 [PMID: 31996915]
  52. Nature. 2017 Aug 17;548(7667):338-342 [PMID: 28792938]

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