Bioinformatics Profiling and Experimental Validation of 4 Differentially-Expressed LIM Genes in the Course of Colorectal-Adenoma-Carcinoma.

Abstract

BACKGROUND LIM domain proteins play crucial roles in tumors by interacting with diverse proteins. However, their roles in the course of colorectal mucosa-adenoma-carcinoma remain unclear. This study aimed to depict their dynamic expression profiles and elucidate their potential functions in this transition course. MATERIAL AND METHODS Differentially-expressed LIM proteins (DELGs) in paired adenomas, carcinomas, and mucosae were identified using the GEO dataset (GSE 117606) and validated by immunohistochemistry using our tissue microarray. Kaplan-Meier survival analysis, WGCNA, module-trait analysis, and KEGG enrichment were conducted. The correlation of DELGs expression levels with immune infiltration was assessed using the ESTIMATE package and TISCH database. The role of DELGs of interest was validated using cell proliferation, migration, and invasion assays. RESULTS Four DELGs were identified - LMO3, FHL1, NEBL, and TGFB1I1 - all of which were of significance in prognosis. Module-trait correlation and KEGG enrichment revealed their involvement in cancer-related signaling. Immunohistochemistry showed gradual downregulation of LMO3 but upregulation of NEBL in the mucosa-adenoma-carcinoma sequence. The opposite expression patterns were observed for FHL1 and TGFB1I1 in tumor epithelium and mesenchyme. High expression levels of the DELGs were correlated with increased infiltration of NK, NKT, and macrophages, except for NEBL. Importantly, LMO3 inhibited proliferation, migration, and invasion of colon epithelial cells. CONCLUSIONS This study identified 4 differentially-expressed LIM genes - LMO3, FHL1, TGFB1I1, and NEBL - and revealed they were involved in the mucosa-adenoma-carcinoma sequence via regulating cancer-related pathways, influencing epigenetic field, or affecting immune infiltration. Our findings provide new insights into the roles of LIM proteins in the course of mucosa-adenoma-carcinoma.

• Authors: Ying He, Zongfu Pan, Qian Shi, Xilin Zhang, Weiyun Shen, Lixia Huo, Huihui Guo, Chengwu Tang, Yuhang Ling
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 28 Pg. e937081 (Jul 20 2022) ISSN: 1643-3750 [Electronic] United States
• PMID: 35854639 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Carrier Proteins
• Cytoskeletal Proteins
• FHL1 protein, human
• Intracellular Signaling Peptides and Proteins
• LIM Domain Proteins
• LMO3 protein, human
• Muscle Proteins
• NEBL protein, human
• TGFB1I1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Adenoma (genetics, metabolism, pathology)
• Carrier Proteins (genetics, metabolism)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Computational Biology (methods)
• Cytoskeletal Proteins (genetics, metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• LIM Domain Proteins (genetics, metabolism)
• Muscle Proteins (genetics, metabolism)