Abstract
Background: LIM domain-containing protein 2 (LIMD2) is known to promote metastasis in several cancers. However, its role and underlying mechanisms in colon cancer remain unclear. This study focused on investigating the prognostic value, functional impact, and molecular mechanisms of LIMD2 in colon cancer. Methods: LIMD2 expression in colon cancer tissues and matched non-cancerous tissues was detected using RT-qPCR and immunohistochemistry. The chi-square test was used to assess the association between LIMD2 expression and clinicopathological characteristics. Kaplan-Meier survival analysis and Cox proportional hazards models were applied to evaluate the prognostic value of LIMD2. The functional role of LIMD2 in colon cancer cell migration was examined through Transwell and wound healing assays. Additionally, RNA sequencing (RNA-seq), co-immunoprecipitation (CoIP), silver staining, and mass spectrometry were performed to uncover the role of LIMD2 in colon cancer cell migration. Results: LIMD2 expression was significantly increased in colon cancer samples and cell lines. High LIMD2 expression was positively correlated with lymph node metastasis and TNM stage. Patients with elevated LIMD2 expression exhibited poorer overall survival (OS). Gain-of-function assays demonstrated that LIMD2 accelerated colon cancer cell migration. RNA-seq analysis revealed that LIMD2 regulates ECM-receptor interactions and focal adhesion pathways. Furthermore, CoIP and mass spectrometry identified cofilin1 as a LIMD2-interacting protein. Conclusions: Our findings indicate that LIMD2 serves as a novel prognostic biomarker and potential target for colon cancer treatment.