RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4
Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical sample...
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Veröffentlicht in: | Cancer gene therapy 2021-05, Vol.28 (5), p.455-470 |
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description | Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease. |
doi_str_mv | 10.1038/s41417-020-00231-2 |
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As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/s41417-020-00231-2</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13 ; 631/337 ; 631/67 ; Biomedical and Life Sciences ; Biomedicine ; Gene Expression ; Gene Therapy</subject><ispartof>Cancer gene therapy, 2021-05, Vol.28 (5), p.455-470</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1642-90ea77d2a5b121afde704c2dd06abcf0a56aeff24b636ac847b5c88ce2fbc8803</citedby><cites>FETCH-LOGICAL-c1642-90ea77d2a5b121afde704c2dd06abcf0a56aeff24b636ac847b5c88ce2fbc8803</cites><orcidid>0000-0002-1436-8362</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41417-020-00231-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41417-020-00231-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Song, Tieniu</creatorcontrib><creatorcontrib>Zhou, Hui</creatorcontrib><creatorcontrib>Wei, Xiaoping</creatorcontrib><creatorcontrib>Meng, Yuqi</creatorcontrib><creatorcontrib>Guo, Quanwei</creatorcontrib><title>RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><description>Lung cancer remains the principal cause of cancer-related death worldwide. 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Zhou, Hui ; Wei, Xiaoping ; Meng, Yuqi ; Guo, Quanwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1642-90ea77d2a5b121afde704c2dd06abcf0a56aeff24b636ac847b5c88ce2fbc8803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>13</topic><topic>631/337</topic><topic>631/67</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Tieniu</creatorcontrib><creatorcontrib>Zhou, Hui</creatorcontrib><creatorcontrib>Wei, Xiaoping</creatorcontrib><creatorcontrib>Meng, Yuqi</creatorcontrib><creatorcontrib>Guo, Quanwei</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Tieniu</au><au>Zhou, Hui</au><au>Wei, Xiaoping</au><au>Meng, Yuqi</au><au>Guo, Quanwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4</atitle><jtitle>Cancer gene therapy</jtitle><stitle>Cancer Gene Ther</stitle><date>2021-05-01</date><risdate>2021</risdate><volume>28</volume><issue>5</issue><spage>455</spage><epage>470</epage><pages>455-470</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><abstract>Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><doi>10.1038/s41417-020-00231-2</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1436-8362</orcidid></addata></record> |
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title | RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4 |
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