For example, by binding to Rab13, MICAL-L2 triggers the transportation of glucose transporter-4 (GLUT4) and mediates GLUT4-containing vesicle localization and fusion with the muscle cell membrane. MICAL-L2 exerts its multiple biological functions primarily via processes involving cargo transportation.
The CH and LIM domains link MICAL-L2 to the actin cytoskeleton, while the CC domain is required for interaction with Rab GTPases. MICAL-like protein 2 (MICAL-L2), a member of the MICAL family, has three conserved domains, namely, a calponin homology (CH) domain a Lin11, Isl-1, and Mec-3 (LIM) domain and a C-terminal coiled-coil (CC) domain. Molecules interacting with CasL (MICALs) represent an evolutionarily conserved family of proteins with roles in the regulation of cytoske leton dynamics. These observations underline the need to further unravel the mechanisms underlying colon cancer progression and identify novel therapeutic targets for the treatment of this disease. Although the 5-year survival rate of patients in the early stages of colon cancer can be higher than 90%, that of patients diagnosed at an advanced stage is lower than 20%. As the tumor volume increases, patients may display abdominal distension and dyspepsia, and may even be able to feel a lump/mass in the abdomen. Patients in the early stage of colon cancer may not present obvious clinical symptoms.
The etiology of colon cancer is mainly associated with a high-fat diet, colonic polyps, genetic make-up, and chronic inflammation. It usually affects adults at 40–50 years of age and occurs more often in males than females. Our results suggested that MICAL-L2 is a promising biomarker for determining prognosis and correlated with immune infiltration levels in COAD.Ĭolon cancer is a commonly diagnosed malignant tumor of the digestive tract and a leading cause of cancer-related death worldwide. Regarding immune infiltration levels, MICAL-L2 was found to be positively associated with CD56 bright NK cells. Functional enrichment analyses revealed that transport-related activity was closely associated with the role of MICAL-L2 in COAD. ROC analysis confirmed the diagnostic value of MICAL-L2, and a prognostic nomogram involving age, M stage, and MICAL-L2 expression was constructed for OS. Furthermore, multivariate Cox analysis indicated that MICAL-L2 was an independent risk factor for OS in COAD patients. Kaplan–Meier survival analysis revealed that patients with MICAL-L2 had shorter OS and DSS. Resultsĭata from TCGA, HPA, and UALCAN datasets indicated that MICAL-L2 expression was significantly higher in COAD tissue than in adjacent normal tissues, and this was confirmed by immunohistochemical assays. In addition, the correlation between MICAL-L2 expression and immune cell infiltration levels was investigated via single-sample gene set enrichment analysis (ssGSEA). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were further utilized to explore the possible cellular mechanism underlying the role of MICAL-L2 in COAD. Univariate and multivariate analysis was employed to determine whether MICAL-L2 could serve as an independent prognostic indicator of OS. Overall survival (OS) and disease-specific survival (DSS) of COAD patients were assessed based on the MICAL-L2 expression level using the Kaplan–Meier method.
The mRNA and protein expression of MICAL-L2 was investigated using TCGA, UALCAN, and independent immunohistochemical assays. In this study, we analyzed the role of MICAL-L2 in COAD using datasets available from public databases. However, the role of MICAL-L2 in colon adenocarcinoma (COAD) has not been well characterized. MICAL-like protein 2 (MICAL-L2), a member of the molecules interacting with CasL (MICAL) family of proteins, is strongly associated with the malignancy of multiple types of cancer.
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