miR-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting Akirin1.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Lung Neoplasms*/genetics ; Lung Neoplasms*/pathology ; Lung Neoplasms*/metabolism ; Cell Movement*/genetics ; Cancer-Associated Fibroblasts*/metabolism ; Cancer-Associated Fibroblasts*/pathology ; Gene Expression Regulation, Neoplastic* ; Neoplasm Invasiveness*; Humans ; Animals ; Mice ; Cell Line, Tumor ; Coculture Techniques

Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
Cancer-associated fibroblasts (CAFs) actively contribute to the formation of tumor-supportive microenvironments, thereby promoting cancer progression and impacting therapeutic outcomes. This study utilized global microRNA (miRNA) expression profiling to identify specific miRNAs responsible for reprogramming normal lung fibroblasts (LFs) into CAFs. miR-224 demonstrates increased expression in CAFs, and its levels are elevated in lung tumors compared to those in normal tissues, according to data from public databases. Overexpression of miR-224 in LFs increases the overall expression of CAF activation markers. Furthermore, LFs overexpressing miR-224 enhanced the migration and invasion of lung cancer cells via direct cell-to-cell contact in a co-culture system. In a mouse orthotopic injection model, miR-224 overexpression in LFs increased lung cancer metastasis. Using target prediction tools and subsequent 3'-UTR luciferase assay, Akirin1 was validated as a direct target gene of miR-224. In addition, LFs depleted of Akirin1 by siRNAs stimulated the migration and invasion of lung cancer cells compared to control LFs. Overall, these findings indicate that miR-224 induces CAF activation and promotes the migration and invasion of lung cancer cells by targeting Akirin1 in co-culture systems.
(© 2025. The Author(s).)

Exp Cell Res. 2008 Mar 10;314(5):1013-29. (PMID: 18255059)
J Cell Biochem. 2019 Jul;120(7):11284-11304. (PMID: 30746755)
Sci Rep. 2018 Jun 11;8(1):8838. (PMID: 29892003)
J Cell Mol Med. 2021 Jun;25(12):5457-5469. (PMID: 33943003)
Int J Cancer. 2022 Oct 15;151(8):1195-1215. (PMID: 35603909)
Cancer Lett. 2021 Jun 28;508:92-103. (PMID: 33775710)
Cancers (Basel). 2015 Oct 14;7(4):2054-62. (PMID: 26473929)
Mol Ther Nucleic Acids. 2024 Apr 23;35(2):102194. (PMID: 38766528)
Mol Cancer. 2017 Feb 7;16(1):35. (PMID: 28173803)
J Cancer Res Ther. 2010 Oct-Dec;6(4):521-9. (PMID: 21358093)
Biochem Biophys Res Commun. 2014 Feb 14;444(3):382-6. (PMID: 24468084)
Oncotarget. 2017 Jun 28;8(44):76116-76128. (PMID: 29100297)
Nat Immunol. 2008 Jan;9(1):97-104. (PMID: 18066067)
Carcinogenesis. 2021 Oct 5;42(9):1143-1153. (PMID: 34170291)
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4288-97. (PMID: 26187928)
Mol Ther Nucleic Acids. 2021 Feb 03;23:1217-1228. (PMID: 33664999)
EMBO J. 2014 Oct 16;33(20):2332-48. (PMID: 25107474)
Biochim Biophys Acta. 2015 Dec;1856(2):189-210. (PMID: 26297204)
Acta Physiol (Oxf). 2014 Aug;211(4):617-33. (PMID: 24938737)
Nat Cell Biol. 2007 Dec;9(12):1392-400. (PMID: 18037882)
Biomed Pharmacother. 2021 Jun;138:111450. (PMID: 33690088)
Nat Cell Biol. 2017 Mar;19(3):224-237. (PMID: 28218910)
Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18691-6. (PMID: 25512506)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
Int J Mol Sci. 2020 Oct 11;21(20):. (PMID: 33050576)
Mol Cancer Res. 2011 Jan;9(1):25-35. (PMID: 21115742)
Cancer Cell. 2012 Mar 20;21(3):309-22. (PMID: 22439926)
J Biol Chem. 2008 Jul 4;283(27):18753-64. (PMID: 18460465)
Anticancer Res. 2013 Sep;33(9):3715-23. (PMID: 24023301)
Cell Rep. 2014 Jun 12;7(5):1664-1678. (PMID: 24857661)
Urol Int. 2022;106(11):1185-1194. (PMID: 34515239)
Cell Rep. 2021 Apr 20;35(3):109009. (PMID: 33882319)
Curr Biol. 2020 Aug 17;30(16):R921-R925. (PMID: 32810447)
Aging (Albany NY). 2021 Apr 4;13(7):10431-10449. (PMID: 33819917)
Cancer Biomark. 2022;34(3):431-441. (PMID: 35275522)
Sci Rep. 2019 Jan 22;9(1):292. (PMID: 30670761)
Cell Physiol Biochem. 2018;48(4):1735-1746. (PMID: 30078003)
Cell Commun Signal. 2020 Apr 7;18(1):59. (PMID: 32264958)
Oncotarget. 2015 Jun 10;6(16):14300-17. (PMID: 25973543)

NRF-2020R1A5A2019210 National Research Foundation of Korea

0 (MicroRNAs)
0 (MIRN224 microRNA, human)

Date Created: 20250124 Date Completed: 20250124 Latest Revision: 20250408

20250408

PMC11760386

10.1038/s41598-024-82189-x

39856124