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一个预测结直肠癌复发的三基因特征揭示了LEMD1通过RhoA/ROCK1信号通路促进结直肠癌细胞迁移。

A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway.

作者信息

Zhang Hui, Xu Chenxin, Jiang Feng, Feng Jifeng

机构信息

Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

Research Center for Clinical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

出版信息

Front Oncol. 2022 May 10;12:823696. doi: 10.3389/fonc.2022.823696. eCollection 2022.

DOI:10.3389/fonc.2022.823696
PMID:35619906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9127067/
Abstract

OBJECTIVE

Colorectal 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.

METHODS

Multiple 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 experiments further validated the potential role of the hub genes in CRC.

RESULTS

A 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 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.

CONCLUSIONS

In 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.

摘要

目的

经历早期复发的结直肠癌（CRC）患者生存率一直较差。然而，尚未开发出有效的方法用于术后复发性CRC的诊断和预后预测。

方法

利用来自GEO数据库和TCGA数据库的多个数据集进行生物信息学分析。进行加权基因共表达网络分析（WGCNA）和秩和分析（RRA）以鉴定关键基因。使用COX/Lasso回归模型构建复发模型。随后的实验进一步验证了核心基因在CRC中的潜在作用。

结果

对多个CRC数据集进行了综合分析，并构建了一个包含LEMD1、SERPINE1和SIAE的CRC复发模型。在两个独立数据库中进一步验证后，我们选择LEMD1进行实验，发现LEMD1可调节CRC细胞的增殖、迁移、侵袭，并促进上皮-间质转化（EMT）。Rho-GTPase下拉实验进一步表明LEMD1可影响RhoA活性并调节细胞骨架动力学。最后，我们证明LEMD1通过RhoA/ROCK1信号通路促进CRC细胞迁移。

结论

在本研究中，通过对多个CRC数据集的综合分析构建了一个由LEMD1、SERPINE1和SIAE组成的CRC复发模型。LEMD1可通过RhoA/ROCK信号通路促进CRC细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc0a/9127067/85a4cf39294e/fonc-12-823696-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc0a/9127067/85a4cf39294e/fonc-12-823696-g008.jpg
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