LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1
Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this st...
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| Veröffentlicht in: | Carcinogenesis (New York) 2024-05, Vol.45 (5), p.311-323 |
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| creator | Pan, Cheng Wang, Qi Wang, Hongshun Deng, Xiaheng Chen, Liang Li, Zhihua |
| description | Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P < 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin-proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD. |
| doi_str_mv | 10.1093/carcin/bgad097 |
| format | Article |
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However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P < 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin-proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgad097</identifier><identifier>PMID: 38153696</identifier><language>eng</language><publisher>England</publisher><subject>Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - metabolism ; Adenocarcinoma of Lung - pathology ; Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Mice ; Mice, Nude ; Prognosis ; RNA, Long Noncoding - genetics ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tripartite Motif Proteins - genetics ; Tripartite Motif Proteins - metabolism ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination</subject><ispartof>Carcinogenesis (New York), 2024-05, Vol.45 (5), p.311-323</ispartof><rights>The Author(s) 2023. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c250t-89baa8c606403a8c433b00d5ba9b2df8f8e8aa758b025a337af9e30ab4d272b43</cites><orcidid>0000-0002-7985-4273 ; 0000-0003-4820-4603</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38153696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pan, Cheng</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Wang, Hongshun</creatorcontrib><creatorcontrib>Deng, Xiaheng</creatorcontrib><creatorcontrib>Chen, Liang</creatorcontrib><creatorcontrib>Li, Zhihua</creatorcontrib><title>LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P < 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin-proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD.</description><subject>Adenocarcinoma of Lung - genetics</subject><subject>Adenocarcinoma of Lung - metabolism</subject><subject>Adenocarcinoma of Lung - pathology</subject><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Prognosis</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tripartite Motif Proteins - genetics</subject><subject>Tripartite Motif Proteins - metabolism</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1PwzAMxSMEYmNw5Yhy5NLNadI2OU4bH5PGkMaQuFVOm5agLd2a9rD_nk4dnGzJPz_7PULuGYwZKD7JsM6sm-gSc1DJBRkyEUMQMgmXZAhM8IBzLgbkxvsfABbzSF2TAZcs4rGKh-SwdNl6NaWz6Xoug-kHo77d72vjvfF027qSYm5c1Z-pdkj3dVWexrZyVB-pcd_oulFJN-vFWxgFO5NbbExOW20PrW2sw-bEVgXdfK3Wc3ZLrgrcenN3riPy-fy0mb0Gy_eXxWy6DLIwgiaQSiPKLIZYAO8awbkGyCONSod5IQtpJGISSQ1hhJwnWCjDAbXIwyTUgo_IY6_bfXxojW_SnfWZ2W7Rmar1aaggYUqIJOrQcY9mdeV9bYp0X9sd1seUQXqKOe39p-eYu4WHs3arO8P_-F-u_Bd2vnr0</recordid><startdate>20240519</startdate><enddate>20240519</enddate><creator>Pan, Cheng</creator><creator>Wang, Qi</creator><creator>Wang, Hongshun</creator><creator>Deng, Xiaheng</creator><creator>Chen, Liang</creator><creator>Li, Zhihua</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7985-4273</orcidid><orcidid>https://orcid.org/0000-0003-4820-4603</orcidid></search><sort><creationdate>20240519</creationdate><title>LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1</title><author>Pan, Cheng ; Wang, Qi ; Wang, Hongshun ; Deng, Xiaheng ; Chen, Liang ; Li, Zhihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c250t-89baa8c606403a8c433b00d5ba9b2df8f8e8aa758b025a337af9e30ab4d272b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenocarcinoma of Lung - genetics</topic><topic>Adenocarcinoma of Lung - metabolism</topic><topic>Adenocarcinoma of Lung - pathology</topic><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Prognosis</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tripartite Motif Proteins - genetics</topic><topic>Tripartite Motif Proteins - metabolism</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pan, Cheng</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Wang, Hongshun</creatorcontrib><creatorcontrib>Deng, Xiaheng</creatorcontrib><creatorcontrib>Chen, Liang</creatorcontrib><creatorcontrib>Li, Zhihua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pan, Cheng</au><au>Wang, Qi</au><au>Wang, Hongshun</au><au>Deng, Xiaheng</au><au>Chen, Liang</au><au>Li, Zhihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2024-05-19</date><risdate>2024</risdate><volume>45</volume><issue>5</issue><spage>311</spage><epage>323</epage><pages>311-323</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><abstract>Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P < 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin-proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD.</abstract><cop>England</cop><pmid>38153696</pmid><doi>10.1093/carcin/bgad097</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7985-4273</orcidid><orcidid>https://orcid.org/0000-0003-4820-4603</orcidid></addata></record> |
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| subjects | Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology Animals Cell Line, Tumor Cell Movement Cell Proliferation Disease Progression Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Mice Mice, Nude Prognosis RNA, Long Noncoding - genetics Transcription Factors - genetics Transcription Factors - metabolism Tripartite Motif Proteins - genetics Tripartite Motif Proteins - metabolism Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination |
| title | LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1 |
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