ABSTRACT
The length of IGF1R 3'UTR is greater than 7 kb. The structure of IGF1R 3'UTR is complex, with multiple binding sites of miRNAs. IGF1R is involved in the regulation of MAPK and PI3K/AKT signaling pathways and theformation and development of tumors. Bioinformatics analysis can reveal the structure features of IGF1R, which provides ideas for further research. The analysis shows that the binding sites between IGF1R and miRNAs have the highest mutation rate in Neuroblastoma. We analyzed the structure of 3'UTR, miRNAs binding sites, physical and chemical properties, hydrophilic-hydrophobic property, glycosylation and phosphorylation sites, secondary structure and tertiary structure modeling of IGF1R. The locations and names of amino acids interacting in IGF1R and IGF1 were obtained by molecular docking. Therefore, if IGF1R 3'UTR is mutated, the capacity of IGF1R combined with miRNAs will reduce and the IGF1R expression will be up-regulated, and the function of miRNAs will be repressed. We can change the sites of IGF1R to combine with IGF1 to repress the function of IGF1R and IGF1. Then the function of IGF1R will be repressed.
Subject(s)
Humans , Binding Sites , Computational Biology , Insulin-Like Growth Factor I , MicroRNAs , Chemistry , Molecular Docking Simulation , Protein Structure, Secondary , Protein Structure, Tertiary , Receptor, IGF Type 1 , Chemistry , Signal TransductionABSTRACT
Objective:To investigate the expression of IGF-IR and PKC and their clinical significance in laryngeal squamous cell carcinoma(LSCC).Method:The expression of IGF-IR and PKC protein were detected by immunohistochemistry and Western blot in 60 cases of LSCC, 25 cases of adjacent non-tumorous laryngeal epithelium and 10 cases of normal laryngeal epithelium.Result:The positive rate of IGF-IR and PKC expression in LSCC were significantly higher than that in normal laryngeal epithelium and adjacent non-tumorous laryngeal epithelium(P<0.05). IGF-IR positive expression were increased more in cases with stage Ⅲ-Ⅳ, cervical lymph node metastasis and well differentiation than that in cases with stageⅠ-Ⅱ, non-lymph node metastasis and poor/mediate differentiation, respectively(P<0.05).The positive rate of PKC in LSCC were correlated with clinical stage and cervical lymph node metastasis.There was a correlation between the expression of IGF-IR and PKC in LSCC.Conclusion:The overexpression of IGF-IR and PKC in the laryngeal carcinoma may play an important role in the carcinogenesis and development of LSCC. It is suggested that detecting the expression of IGF-IR and PKC can be used for early diagnosis and treatment of LSCC.
ABSTRACT
The activation of the insulin-like growth factor-I-receptor system (IGF-IR) has recently emerged as critical events in transformation and tumorigenicity of several human tumors. In this study we investigated the expression of IGF-IR in 33 colorectal adenomas, 88 primary colorectal carcinomas, and 30 normal colonic mucosa adjacent to the carcinoma. Immunohistochemical staining (IHC) for IGF-IR was performed on paraffin embedded sections using an anti-IGF-IR rabbit polyclonal antibody. IHC stains for IGF-IR were scored using a semiquantitative scoring system. The relationship of IGF-IR staining to clinicopathologic variables and proliferating cell nuclear antigen (PCNA) staining was also analysed. The mean IHC scores for IGF-IR of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 0.41 0.96, 0.76 1.23, 2.0 1.48, 2.83 2.0 and 5.93 1.58, respectively. These scores for each category were statistically significant except between normal glands and adenoma and between intramucosal carcinoma and node-negative carcinomas. The mean PCNA indexes of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 2.48 2.60, 6.94 11.03, 27.21 11.42, 43.36 9.9 and 57.60 10.01, respectively. The PCNA index for each category was statistically significant except between normal and adenoma. IGF-IR scores and PCNA indexes were higher with tumor progression and also correlated each other (sr=0.65, p=0.0001). Higher IGF-IR scores and PCNA indexes were seen in tumors with advanced stage, infiltrative growth pattern, poor differentiation, nerve invasion, lymphovascular invasion, and moderate fibrosis. Our results suggest that IGF-IR plays an important role in tumorigenicity and tumor progression.