LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis
Abstract Background Metastasis is a leading cause of colorectal cancer (CRC)-related mortality, yet its molecular mechanisms remain poorly understood. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of CRC metastasis, but their specific roles are not fully elucidated. This study id...
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BMC
2025-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03368-w |
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| author | Junwen Qi Tao Jiang Bowen Liu Qihang Hu Junnan Chen Ning Ma Yixin Xu Hu Song Jun Song |
| author_facet | Junwen Qi Tao Jiang Bowen Liu Qihang Hu Junnan Chen Ning Ma Yixin Xu Hu Song Jun Song |
| author_sort | Junwen Qi |
| collection | DOAJ |
| description | Abstract Background Metastasis is a leading cause of colorectal cancer (CRC)-related mortality, yet its molecular mechanisms remain poorly understood. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of CRC metastasis, but their specific roles are not fully elucidated. This study identifies and characterizes a novel lncRNA LINC02167 as a critical regulator of CRC metastasis. Methods LINC02167 expression was analyzed in CRC tissues via real-time quantitative polymerase chain reaction and fluorescence in situ hybridization. Functional assays evaluated its role in CRC cell migration, invasion, and metastasis in vitro and in vivo. Mechanistic exploration involves a combination of techniques, including RNA sequencing, mass spectrometry, RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assays, RNA stability assays, and bioinformatics analysis, to uncover the molecular interactions and pathways regulated by LINC02167. Results LINC02167 is markedly upregulated in CRC tissues and strongly correlates with advanced clinical features and poor prognosis. Functional analyses reveal that LINC02167 enhances CRC cell migration and invasion in vitro and promotes metastasis in vivo. Mechanistically, LINC02167 serves as a molecular scaffold, forming a complex with YBX1 and ILF3 to facilitate YBX1 binding to NSUN2-mediated m5C modification sites on KSR1 mRNA, thereby stabilizing KSR1 mRNA and activating the ERK/MAPK signaling pathway to drive CRC metastasis. Additionally, MYC-driven transcriptional activation leads to the upregulation of LINC02167 in CRC. Conclusions This study uncovers a novel mechanism through which LINC02167 promotes the ERK/MAPK pathway and CRC metastasis via m5C modification, underscoring its potential as a promising therapeutic target for metastatic CRC treatment. |
| format | Article |
| id | doaj-art-e5c201cfda1344ef80f93152dbe5bbb1 |
| institution | DOAJ |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-e5c201cfda1344ef80f93152dbe5bbb12025-08-20T03:18:31ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-04-0144112210.1186/s13046-025-03368-wLINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasisJunwen Qi0Tao Jiang1Bowen Liu2Qihang Hu3Junnan Chen4Ning Ma5Yixin Xu6Hu Song7Jun Song8Affiliated First Clinical College, Xuzhou Medical University, XuzhouDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical University, XuzhouDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical University, XuzhouAffiliated First Clinical College, Xuzhou Medical University, XuzhouAffiliated First Clinical College, Xuzhou Medical University, XuzhouAffiliated First Clinical College, Xuzhou Medical University, XuzhouDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical University, XuzhouDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical University, XuzhouDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical University, XuzhouAbstract Background Metastasis is a leading cause of colorectal cancer (CRC)-related mortality, yet its molecular mechanisms remain poorly understood. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of CRC metastasis, but their specific roles are not fully elucidated. This study identifies and characterizes a novel lncRNA LINC02167 as a critical regulator of CRC metastasis. Methods LINC02167 expression was analyzed in CRC tissues via real-time quantitative polymerase chain reaction and fluorescence in situ hybridization. Functional assays evaluated its role in CRC cell migration, invasion, and metastasis in vitro and in vivo. Mechanistic exploration involves a combination of techniques, including RNA sequencing, mass spectrometry, RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assays, RNA stability assays, and bioinformatics analysis, to uncover the molecular interactions and pathways regulated by LINC02167. Results LINC02167 is markedly upregulated in CRC tissues and strongly correlates with advanced clinical features and poor prognosis. Functional analyses reveal that LINC02167 enhances CRC cell migration and invasion in vitro and promotes metastasis in vivo. Mechanistically, LINC02167 serves as a molecular scaffold, forming a complex with YBX1 and ILF3 to facilitate YBX1 binding to NSUN2-mediated m5C modification sites on KSR1 mRNA, thereby stabilizing KSR1 mRNA and activating the ERK/MAPK signaling pathway to drive CRC metastasis. Additionally, MYC-driven transcriptional activation leads to the upregulation of LINC02167 in CRC. Conclusions This study uncovers a novel mechanism through which LINC02167 promotes the ERK/MAPK pathway and CRC metastasis via m5C modification, underscoring its potential as a promising therapeutic target for metastatic CRC treatment.https://doi.org/10.1186/s13046-025-03368-wLong noncoding RNAMetastasisKSR15-methylcytosineTranscription |
| spellingShingle | Junwen Qi Tao Jiang Bowen Liu Qihang Hu Junnan Chen Ning Ma Yixin Xu Hu Song Jun Song LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis Journal of Experimental & Clinical Cancer Research Long noncoding RNA Metastasis KSR1 5-methylcytosine Transcription |
| title | LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis |
| title_full | LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis |
| title_fullStr | LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis |
| title_full_unstemmed | LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis |
| title_short | LINC02167 stabilizes KSR1 mRNA in an m5C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis |
| title_sort | linc02167 stabilizes ksr1 mrna in an m5c dependent manner to regulate the erk mapk signaling pathway and promotes colorectal cancer metastasis |
| topic | Long noncoding RNA Metastasis KSR1 5-methylcytosine Transcription |
| url | https://doi.org/10.1186/s13046-025-03368-w |
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