BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma.

Yibing Li, Jianing Huo, Junjian He, Yunzheng Zhang, Xiaoxin Ma
Author Information
  1. Yibing Li: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China.
  2. Jianing Huo: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China.
  3. Junjian He: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China.
  4. Yunzheng Zhang: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China.
  5. Xiaoxin Ma: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110000 Liaoning People's Republic of China. ORCID

Abstract

BACKGROUND: Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC.
METHODS: Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot.
RESULTS: We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs.
CONCLUSIONS: BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.

Keywords

References

  1. Oncotarget. 2015 Aug 14;6(23):19685-705 [PMID: 26050197]
  2. J Exp Clin Cancer Res. 2020 May 7;39(1):81 [PMID: 32381043]
  3. Neoplasia. 2007 Feb;9(2):166-80 [PMID: 17356713]
  4. FEBS Lett. 2002 Feb 20;513(1):38-44 [PMID: 11911878]
  5. Cell Death Dis. 2018 Feb 21;9(3):303 [PMID: 29467441]
  6. Oncol Rep. 2015 Dec;34(6):3017-24 [PMID: 26503430]
  7. Tumour Biol. 2014 Dec;35(12):11771-9 [PMID: 25173640]
  8. Cell Death Dis. 2018 May 3;9(5):509 [PMID: 29724991]
  9. J Cell Biochem. 2019 Aug;120(8):13310-13320 [PMID: 30916818]
  10. Mol Biol Rep. 2014 Sep;41(9):5979-88 [PMID: 24985971]
  11. Nucleic Acids Res. 2018 Jan 4;46(D1):D956-D963 [PMID: 29136207]
  12. J Clin Med. 2020 Jun 17;9(6): [PMID: 32560580]
  13. Recent Pat Anticancer Drug Discov. 2020;15(1):78-85 [PMID: 31916520]
  14. Oncol Rep. 2013 Nov;30(5):2137-44 [PMID: 23982470]
  15. Am Fam Physician. 2016 Mar 15;93(6):468-74 [PMID: 26977831]
  16. Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102 [PMID: 28407145]
  17. J Cell Physiol. 2019 Jul;234(7):11999-12010 [PMID: 30515803]
  18. Front Med. 2018 Aug;12(4):361-373 [PMID: 30043221]
  19. Nucleic Acids Res. 2015 Jan;43(Database issue):D146-52 [PMID: 25378301]
  20. Sci Rep. 2018 Nov 1;8(1):16167 [PMID: 30385776]
  21. Int J Ayurveda Res. 2010 Oct;1(4):274-8 [PMID: 21455458]
  22. Int J Oncol. 2015 Feb;46(2):641-8 [PMID: 25405901]
  23. Cancer Cell Int. 2020 Aug 3;20:363 [PMID: 32774157]
  24. CA Cancer J Clin. 2019 Jan;69(1):7-34 [PMID: 30620402]
  25. Int J Biol Markers. 2018 May;33(2):189-194 [PMID: 29076521]
  26. J Cell Physiol. 2019 May;234(5):5379-5389 [PMID: 30350856]
  27. Theranostics. 2017 Sep 5;7(16):3920-3932 [PMID: 29109788]
  28. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2760-5 [PMID: 21930940]
  29. Oncol Lett. 2019 Sep;18(3):2825-2834 [PMID: 31452761]
  30. Neoplasia. 2017 Aug;19(8):649-658 [PMID: 28732212]
  31. Dig Liver Dis. 2013 May;45(5):422-9 [PMID: 23332081]
  32. Mol Med Rep. 2014 Jun;9(6):2374-80 [PMID: 24714932]
  33. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1100-5 [PMID: 20080567]
  34. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20 [PMID: 20576703]
  35. J Cell Physiol. 2010 Jan;222(1):66-72 [PMID: 19746446]
  36. Int J Mol Med. 2015 Mar;35(3):777-83 [PMID: 25571854]
  37. CA Cancer J Clin. 2019 May;69(3):184-210 [PMID: 30875085]
  38. J Cell Physiol. 2015 Dec;230(12):2881-90 [PMID: 25967096]
  39. Nat Commun. 2019 Apr 3;10(1):1523 [PMID: 30944313]
  40. FEBS J. 2012 Oct;279(19):3715-3726 [PMID: 22863320]
  41. Onco Targets Ther. 2018 Mar 06;11:1275-1284 [PMID: 29563806]
  42. Dig Dis Sci. 2015 May;60(5):1256-64 [PMID: 25487193]
  43. CA Cancer J Clin. 2018 Nov;68(6):394-424 [PMID: 30207593]
  44. Am J Transl Res. 2019 Sep 15;11(9):5404-5416 [PMID: 31632519]
  45. Int J Mol Sci. 2013 Sep 27;14(10):19670-80 [PMID: 24084718]
  46. Int J Oncol. 2017 May;50(5):1778-1784 [PMID: 28339086]
  47. Tumour Biol. 2014 Apr;35(4):2949-57 [PMID: 24264312]
  48. Int J Oncol. 2014 Oct;45(4):1574-82 [PMID: 25017022]
  49. J Natl Compr Canc Netw. 2018 Feb;16(2):170-199 [PMID: 29439178]
  50. Cell Struct Funct. 2019;44(1):29-39 [PMID: 30787206]
  51. Genes Cells. 2002 Jan;7(1):29-39 [PMID: 11856371]

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Created with Highcharts 10.0.0BTG1ECexpressionprognosiscarcinomageneECCsdevelopmentusedanalyzedrelatedinvasionapoptosisEMTEndometrialmalignanttumorsoccurrencevarietyTCGAbioinformaticsusingqRT-PCRproliferationcellbehaviorendometrialprocessblotlowsuggestedanalysisreceptorplaysimportantroleinhibitsBACKGROUND:onethreemajorfemalereproductivesystemrecentyearsincidencemortalityrateincreasedB-celltranslocation1anti-proliferationregulatesresearchregardingMETHODS:BasedCancerGenomeAtlasdatabasetoolsdatabasesexploreverifiedrelevantclinicopathologicalparametersfunctionallyenrichedgenespatientswebsitemiRNAtargetsinteractingproteinnetworksCellwoundhealingtranswellassaysdetecteffectsbiologicalcellseffectepithelial-to-mesenchymaltransitiondetectedwesternRESULTS:basedfoundassociatedpoorsignificantlycorrelatedoverallsurvivalOSshorteningClinicopathologicaldepthInternationalFederationGynecologyObstetricsFIGOstagepathologicaltissuetypefertilityhistorylymphaticmetastasismenopauseestrogenERprogesteronePRagediagnosisFunctionalenrichmentshowedregulatingembryonictumorigenesiscycleBiologicalexperimentssuggestmigrationpromotesWesternindicatedinhibitedCONCLUSIONS:tumorsuppressorbelievecanpotentialprognosticbiomarkermalignancynovelsignatureApoptosisBioinformaticsInvasionMigrationPrognosisProliferation

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