A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway
ObjectiveColorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC.MethodsMultiple datasets from the GEO database and TCGA database were...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.823696/full |
| _version_ | 1811308139972132864 |
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| author | Hui Zhang Chenxin Xu Feng Jiang Jifeng Feng |
| author_facet | Hui Zhang Chenxin Xu Feng Jiang Jifeng Feng |
| author_sort | Hui Zhang |
| collection | DOAJ |
| description | ObjectiveColorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC.MethodsMultiple datasets from the GEO database and TCGA database were utilized for bioinformatics analysis. WGCNA analyses and RRA analysis were performed to identify key genes. The COX/Lasso regression model was used to construct the recurrence model. Subsequent in vitro experiments further validated the potential role of the hub genes in CRC.ResultsA comprehensive analysis was performed on multiple CRC datasets and a CRC recurrence model was constructed containing LEMD1, SERPINE1, and SIAE. After further validation in two independent databases, we selected LEMD1 for in vitro experiments and found that LEMD1 could regulate CRC cell proliferation, migration, invasion, and promote EMT transition. The Rho-GTPase pulldown experiments further indicated that LEMD1 could affect RhoA activity and regulate cytoskeletal dynamics. Finally, we demonstrated that LEMD1 promoted CRC cell migration through the RhoA/ROCK1 signaling pathway.ConclusionsIn this study, a CRC relapse model consisting of LEMD1, SERPINE1, and SIAE was constructed by comprehensive analysis of multiple CRC datasets. LEMD1 could promote CRC cell migration through the RhoA/ROCK signaling pathway. |
| first_indexed | 2024-04-13T09:16:48Z |
| format | Article |
| id | doaj.art-64ea6999c75247058929e54232f0d2f3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T09:16:48Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-64ea6999c75247058929e54232f0d2f32022-12-22T02:52:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.823696823696A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling PathwayHui Zhang0Chenxin Xu1Feng Jiang2Jifeng Feng3Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaResearch Center for Clinical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaJiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaResearch Center for Clinical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, ChinaObjectiveColorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC.MethodsMultiple datasets from the GEO database and TCGA database were utilized for bioinformatics analysis. WGCNA analyses and RRA analysis were performed to identify key genes. The COX/Lasso regression model was used to construct the recurrence model. Subsequent in vitro experiments further validated the potential role of the hub genes in CRC.ResultsA comprehensive analysis was performed on multiple CRC datasets and a CRC recurrence model was constructed containing LEMD1, SERPINE1, and SIAE. After further validation in two independent databases, we selected LEMD1 for in vitro experiments and found that LEMD1 could regulate CRC cell proliferation, migration, invasion, and promote EMT transition. The Rho-GTPase pulldown experiments further indicated that LEMD1 could affect RhoA activity and regulate cytoskeletal dynamics. Finally, we demonstrated that LEMD1 promoted CRC cell migration through the RhoA/ROCK1 signaling pathway.ConclusionsIn this study, a CRC relapse model consisting of LEMD1, SERPINE1, and SIAE was constructed by comprehensive analysis of multiple CRC datasets. LEMD1 could promote CRC cell migration through the RhoA/ROCK signaling pathway.https://www.frontiersin.org/articles/10.3389/fonc.2022.823696/fullLEMD1relapse modelRhoAEMTcolorectal cancermetastasis |
| spellingShingle | Hui Zhang Chenxin Xu Feng Jiang Jifeng Feng A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway Frontiers in Oncology LEMD1 relapse model RhoA EMT colorectal cancer metastasis |
| title | A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway |
| title_full | A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway |
| title_fullStr | A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway |
| title_full_unstemmed | A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway |
| title_short | A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway |
| title_sort | three genes signature predicting colorectal cancer relapse reveals lemd1 promoting crc cells migration by rhoa rock1 signaling pathway |
| topic | LEMD1 relapse model RhoA EMT colorectal cancer metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.823696/full |
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