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Studies have confirmed that circular RNA (circRNA) has a stable closed structure, which plays an important role in the progression of tumors. Cancers with positive fusion genes can produce associated fusion circRNA (F-cirRNA). However, there are no reports concerning a role for F-circRNA of the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1 (EML4-ALK1) in non-small cell lung cancer (NSCLC). Our study confirmed the existence of fusion circEA1 (F-circEA1) in NCI-H3122 cells (carrying the EML4-ALK1 gene), F-circEA1 was expressed both in the cytoplasm and nucleus as determined by fluorescence in situ hybridization (FISH) and Sanger sequencing. CCK8 and transwell assays showed that F-circEA1 was beneficial to cell proliferation, metastasis, and invasion. Overexpression of F-circEA1 can also promote cell proliferation, migration and invasion in A549 and SPCA1 cells (non-small cell lung cancer cell line not carrying the EML4-ALK1 gene). Interference with F-circEA1, induced cell cycle arrest and promoted apoptosis as determined by flow cytometry, and increased drug sensitivity to crizotinib in H3122 cells. F-circEA1 directly affected the expression of parental gene EML4-ALK1. Further research found that F-circEA1 can affect the downstream signaling pathway of ALK. In vivo, the growth rate of xenogeneic tumors was reduced and the protein expression level of EML4-ALK1 was significantly decreased in transplanted tumors measured by immunohistochemistry (IHC) after interference with F-circEA1. In conclusion, F-circEA1 can be considered as a proto-oncogene that regulates cell proliferation and apoptosis by affecting the expression of the parental gene EML4-ALK1 and its ALK downstream signaling pathway in non-small cell lung cancer.

Titel:	F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer.
Autor/in / Beteiligte Person:	Huo, Y ; Lv, T ; Ye, M ; Zhu, S ; Liu, J ; Liu, H ; Song, Y
Link:	Full Text Finder (Volltext)
Zeitschrift:	Human cell, Jg. 35 (2022), Heft 1, S. 260-270
Veröffentlichung:	2011- : Tokyo : Springer ; <i>Original Publication</i>: Tōkyō-to : Hito Saibō Kenkyūkai : Kanishobo, Shōwa 63-nen [1988]-, 2022
Medientyp:	academicJournal
ISSN:	1749-0774 (electronic)
DOI:	10.1007/s13577-021-00628-7
Schlagwort:	Cell Cycle Proteins genetics Cell Cycle Proteins metabolism Cell Line, Tumor Gene Expression genetics Humans Microtubule-Associated Proteins genetics Microtubule-Associated Proteins metabolism RNA, Circular genetics RNA, Circular metabolism Serine Endopeptidases genetics Serine Endopeptidases metabolism Activin Receptors, Type II genetics Activin Receptors, Type II metabolism Apoptosis genetics Carcinoma, Non-Small-Cell Lung genetics Carcinoma, Non-Small-Cell Lung pathology Cell Proliferation genetics Gene Expression Regulation, Neoplastic genetics Lung Neoplasms genetics Lung Neoplasms pathology RNA, Circular physiology Signal Transduction genetics Signal Transduction physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Hum Cell] 2022 Jan; Vol. 35 (1), pp. 260-270. <i>Date of Electronic Publication: </i>2021 Oct 11. MeSH Terms: Activin Receptors, Type II / genetics ; Activin Receptors, Type II / metabolism ; Apoptosis / genetics ; Carcinoma, Non-Small-Cell Lung / genetics ; Carcinoma, Non-Small-Cell Lung / pathology ; Cell Proliferation / genetics ; Gene Expression Regulation, Neoplastic / genetics ; Lung Neoplasms / genetics ; Lung Neoplasms / pathology ; RNA, Circular / physiology ; Signal Transduction / genetics ; Signal Transduction / physiology ; Cell Cycle Proteins / genetics ; Cell Cycle Proteins / metabolism ; Cell Line, Tumor ; Gene Expression / genetics ; Humans ; Microtubule-Associated Proteins / genetics ; Microtubule-Associated Proteins / metabolism ; RNA, Circular / genetics ; RNA, Circular / metabolism ; Serine Endopeptidases / genetics ; Serine Endopeptidases / metabolism References: Cell Res. 2018 Jun;28(6):693-695. (PMID: 29628502) ; Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230) ; Cell Res. 2015 Aug;25(8):981-4. (PMID: 26138677) ; Blood. 2003 Mar 1;101(5):1919-27. (PMID: 12424201) ; N Engl J Med. 2010 Oct 28;363(18):1727-33. (PMID: 20979472) ; Nature. 2018 Jan 24;553(7689):446-454. (PMID: 29364287) ; Clin Cancer Res. 2011 Apr 15;17(8):2081-6. (PMID: 21288922) ; Clin Chem. 2015 Jan;61(1):221-30. (PMID: 25376581) ; Wiley Interdiscip Rev RNA. 2017 Jul;8(4):. (PMID: 28130830) ; Cancer Res. 2008 Jul 1;68(13):4971-6. (PMID: 18593892) ; Cell. 2016 Aug 11;166(4):1055-1056. (PMID: 27518567) ; Appl Immunohistochem Mol Morphol. 2015 Apr;23(4):239-44. (PMID: 25265433) ; FASEB J. 1997 Oct;11(12):965-72. (PMID: 9337149) ; RNA Biol. 2015;12(4):381-8. (PMID: 25746834) ; Mol Cancer. 2018 Sep 20;17(1):138. (PMID: 30236141) ; Int J Mol Sci. 2014 May 26;15(6):9331-42. (PMID: 24865493) ; Blood. 1997 Oct 15;90(8):2901-10. (PMID: 9376569) ; Mol Cancer. 2019 May 22;18(1):98. (PMID: 31118036) ; Blood. 2005 Dec 1;106(12):3907-16. (PMID: 16105984) ; iScience. 2018 Jul 27;5:19-29. (PMID: 30240643) ; Kardiochir Torakochirurgia Pol. 2018 Jun;15(2):65-71. (PMID: 30069185) ; Am J Cancer Res. 2016 Jun 01;6(6):1167-76. (PMID: 27429839) Grant Information: Grant Nos. 81572273 National Natural Science Foundation of China; No. QNRC2016911 Senior Talent Foundation of Jiangsu University; No. YKK16246 Nanjing Medical Science and Technology Development Project Contributed Indexing: Keywords: Apoptosis; Circular RNA; EML4-ALK; F-circEA1; NSCLC Substance Nomenclature: 0 (Cell Cycle Proteins) ; 0 (Microtubule-Associated Proteins) ; 0 (RNA, Circular) ; EC 2.7.11.30 (ACVRL1 protein, human) ; EC 2.7.11.30 (Activin Receptors, Type II) ; EC 3.4.21.- (EML4 protein, human) ; EC 3.4.21.- (Serine Endopeptidases) Entry Date(s): Date Created: 20211011 Date Completed: 20220204 Latest Revision: 20220218 Update Code: 20231215 PubMed Central ID: PMC8732839

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F-circEA1 regulates cell proliferation and apoptosis through ALK downstream signaling pathway in non-small cell lung cancer.