OBJECTIVETo investigate the impact and mechanism of microRNA (miR)-378 on hepatocellular carcinoma (HCC) cell growth.

METHODSThe human hepatoma cell line HepG2 and its derivative HepG2.2.15 (stably expressing hepatitis B virus (HBV)) were transduced with lentiviruses expressing miR-378 or non-expressing controls (nc-Lv). Effects on cell proliferation were assessed by the MTT assay and on colony-formation efficiency by clonogenic assay. Targets of miR-378 were predicted by bioinformatic analysis and validated by luciferase reporter assay in the human embryonic kidney cell line HEK293. Real-time polymerase chain reaction and western blotting were used to monitor expression of the endogenous targets in miR-378- overexpressing HepG2 and HepG2.2.15 cells.

RESULTSThe HepG2 and HepG2.2.15 cells transduced with lentivirus expressing miR-378 showed significantly lower cell proliferation and colony formation than the control cells transduced with nc-Lv (P less than 0.01 and P less than 0.05, respectively). The insulin-like growth factor 1 receptor (IGF1R) was predicted as a potential target of miR-378, and luciferase reporter activity of IGF1R was significantly decreased in the HEK293 cells co-transfected with miR-378 (by 41.8% vs. the control cells, P less than 0.01). Moreover, the miRNA-378-mediated effect was narrowed down to the 3'-untranslated region (UTR) of IGF1R. The miRNA-378-mediated reduction of IGF1R specifically involved its protein expression (P less than 0.01) and not its mRNA expression (P more than 0.05).

CONCLUSIONmiR-378 may suppress growth characteristics of HBV-related HCC by directly targeting the IGF1R 3'-UTR and inhibiting its protein expression.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Proliferation ; HEK293 Cells ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; MicroRNAs ; genetics ; Receptor, IGF Type 1 ; genetics ; Transfection

OBJECTIVETo study the effects of astragaloside on the expression of insulin-like growth factor-1 (IGF-1) and associated proteins in mice with viral myocarditis.

METHODSSixty-five 4-week-old BALB/C mice were randomly divided into 5 groups: normal control, astragaloside control, untreated myocarditis, low-dose and high-dose astragaloside-treated myocarditis. The BALB/C mice in the later three groups were intraperitoneally injected with CVB3. The low-dose and high-dose astragaloside-treated myocarditis groups were given astragaloside of 0.07 and 0.6 mg/kg•d, respectively by intragastric administration. Fifteen days later, the samples of blood and muscular tissues were obtained. The expression of IGF-1 in plasma was measured using ELISA. The levels of IGF-1 and associated proteins in muscular tissues were measured by immunohistochemistry. The expression of IGF-1 mRNA in muscular tissues was examined by RT-polymerase chain reaction (RT-PCR).

RESULTSThe expression of IGF-1 and associated proteins increased significantly in mice infected with CVB3. High-dose astragaloside treatment reduced the expression of IGF-1 and associated proteins, but low-dose astragaloside did not.

CONCLUSIONSHigh-dose astragaloside may reduce the expression of IGF-1 and associated proteins in mice with acute viral myocarditis, possibly thus providing protective effects on muscular tissues.

Acute Disease ; Animals ; Coxsackievirus Infections ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Enterovirus B, Human ; Insulin-Like Growth Factor Binding Protein 3 ; analysis ; Insulin-Like Growth Factor I ; analysis ; genetics ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; drug therapy ; metabolism ; Myocardium ; chemistry ; RNA, Messenger ; analysis ; Receptor, IGF Type 1 ; analysis ; Saponins ; therapeutic use ; Triterpenes ; therapeutic use

OBJECTIVETo study the association between single nucleotide polymorphism (SNP) of insulin-like growth factor I receptor (IGF-IR) gene and idiopathic short stature (ISS).

METHODSA total of 804 children with ISS and 575 normal controls were recruited from 2008 to 2011. IGF-IR gene SNP was genotyped using the Snapshot Multiplex System.

RESULTSThe distribution frequency of genotype rs1976667 showed no significant difference between the ISS and the control groups, while that of the allele A of rs1976667 was significantly higher in the ISS group than in the control group (P<0.01).

CONCLUSIONSThe allele A at rs1976667 SNP of IGF-IR gene is a risk factor for ISS.

Adolescent ; Child ; Child, Preschool ; Female ; Growth Disorders ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptor, IGF Type 1 ; genetics

OBJECTIVETo explore the correlation of IGF-1R expression with clinical features of esophageal squamous cell carcinoma (ESCC) and to investigate the effect of silencing IGF-1R by siRNA on the proliferation of esophageal cancer cell line EC9706 cells.

METHODSImmunohistochemistry was used to detect the expresion of IGF-1R in 80 specimens of ESCC and 18 specimens of normal esophageal mucosa. IGF-1R siRNA was transfected into esophageal squamous cell carcinoma EC9706 cells, and the effect of RNAi was assessed by Western blot. The proliferation of EC9706 cells was determined by drawing growth curve, MTT assay and plate colony-forming assay.

RESULTSThe total and strong positive rates of IGF-1R expression were 86.3% and 51.3% in ESCC, and 61.1% and 11.1% in normal esophageal epithelium, respectively. The total and strong positive rates of IGF-1R expression in patients with lymph node metastasis were 94.4% and 74.1%, significantly higher than 69.2% and 3.9%, respectively, in those without lymph node metastasis (P<0.01). A significantly higher IGF-1R expression was associated with lower histological grade (P<0.05). The total and strong rates of IGF-1R expression in 39 patients of stages III and IV were 97.4% and 71.8% , significantly higher than the 75.6% and 31.7%, respectively, in 41 cases of stages I and II (P<0.01). IGF-1R RNAi significantly inhibited IGF-1R expression and the growth of EC9706 cells. The clone formation rate of RNAi-IGF-1R transfected cells was 19.1%, significantly lower than that of 52.3% in non-transfected cells and 49.0% in empty vector-transfected EC9706 cells (P<0.05).

CONCLUSIONSThe overexpression of IGF-1R is colerated with lymph node metastasis, differentiation and clinical stage. Down-regulation of IGF-1R can inhibit the proliferation of esophageal cancer EC9706 cells in vitro.

Aged ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Esophageal Neoplasms ; genetics ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA Interference ; RNA, Small Interfering ; genetics ; Receptor, IGF Type 1 ; genetics ; metabolism ; Transfection

OBJECTIVE: To study the expression of insulin-like growth factor-1 receptor(IGF-1R) in nasal polyps and its relationship with allergic rhinitis. METHOD: The mRNA and protein expression of IGF-1R in 40 cases (20 cases with allergic rhinitis and 20 cases without) nasal polyps tissue (the CRSWNP group) and 20 middle turbinate tissue samples (the control group) were examined by fluorescence quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry. RESULT: The positive staining rate of IGF-1R protein of nasal polyps tissue is 70.8% and that of control is 12.3%, the expression of IGF-1R mRNA of nasal polyp is 0.748 +/- 0.111,which is significant higher than that of the control group is 0.107 +/- 0.208 (P < 0.01). No significant difference of the expression of IGF-1R mRNA between with and without allergic rhinitis cases and between with and without endoscopy sinus surgery history cases in the CRSWNP group. CONCLUSION The overexpression of IGF-1R maybe play important roles in the formation of nasal polyp. Hypersensitivity reaction type I mediated by IgE has no contribution to the overexpression of the IGF-1R.
Adult ; Case-Control Studies ; Female ; Humans ; Hypersensitivity ; pathology ; Male ; Middle Aged ; Nasal Polyps ; immunology ; metabolism ; pathology ; RNA, Messenger ; genetics ; Receptor, IGF Type 1 ; metabolism ; Young Adult

A 15q25-qter partial trisomy characterized by pre or postnatal overgrowth, tall stature, macrocephaly and craniosynostosis has rarely been reported. The cause of overgrowth has been thought to be the triplication of the insulin-like growth factor 1 receptor (IGF1R) gene located on the 15q26.3. We report a patient with partial trisomy 15q25.3-qter showing mental retardation, developmental delay, macrocephaly, long narrow face, ptosis, high palate arch, scoliosis, clinodactyly and overgrowth. Additional material located on terminal 2q was found in karyotyping analysis. In bacterial artificial chromosome (BAC) clone-based-array comparative genomic hybridization (aCGH) analysis, a gain of 31 clones on 15q25.3-qter and a loss of 2 clones on 2q37.3 were observed. An extra copy of IGF1R gene was observed on derivative chromosome 2 in FISH analysis. In conclusion, the patient was diagnosed to have de novo 46,XX,der(2)t(2;15)(q37.3;q25.3) chromosome complement. Adequate genetic counseling and regular follow-ups would be needed for the patient.
Abnormalities, Multiple/genetics ; Child, Preschool ; *Chromosomes, Human, Pair 15 ; Comparative Genomic Hybridization ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Receptor, IGF Type 1/*genetics ; Translocation, Genetic ; *Trisomy

OBJECTIVETo investigate the association of insulin-like growth factor-1 receptor (IGF-1R) gene polymorphisms and with susceptibility to adolescent idiopathic scoliosis (AIS).

METHODSThis study included 200 patients with AIS and 200 healthy controls. Height, menarche status, curve pattern, Cobb angle, and Risser sign in female patients were recorded. Blood samples were taken form each subject by venipuncture. Genetic DNA was extract from peripheral blood leukocytes using standard phenol/chloroform extraction. PCR-RFLP (polymerase chain reaction-restriction-fragment length polymorphism) was used for the genotyping.

RESULTThe genotype and allele frequency distribution were similar between AIS and normal control (P>0.05). The mean maximum Cobb angle, Risser sign, menarche status of different genotypes of IGF-1R gene were similar with each other among female AIS patients (P>0.05).

CONCLUSIONSThe IGF-1R gene is neither associated with the occurrence nor the curve severity of AIS.

Adolescent ; Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Receptor, IGF Type 1 ; genetics ; Scoliosis ; genetics ; Young Adult

OBJECTIVETo investigate the biological behaviors and chemosensitivity of non-small cell lung cancer (NSCLC) cell line A549 after IGF-IR gene silencing by RNA interference (RNAi) in vitro.

METHODSTwo plasmids siRNA 1 and 2 expressing IGF-IR siRNA with human U6 promoter were constructed,and an unrelated siRNA was used as negative control. NSCLC A549 cells were transfected with sequence-specific siRNA or unrelated siRNA as control. Quantitative RT-PCR and Western blot were used to detect the expression of IGF-IR. NSCLC A549 cells were transfected with siRNA and treated with DDP. MTT assay and flow cytometry were used to assess the effects of IGF-IR silencing on tumor cell proliferation and chemosensitivity.

RESULTTransfection of NSCLC cells with siRNA resulted in reduction of IGF-IR mRNA expression by 78.9 % and protein production by 89.8%. The decrease in IGF-IR levels caused significant growth inhibition of A549 cells both at 48 h and at 72 h, and decrease of the IC50 of DDP at 24 h, 48 h and at 72 h. Flow cytometry showed that 77.5% of A549 cells retained in G0/G1 phase.

CONCLUSIONThe sequence specific suppression of IGF-IR gene expression by RNAi enhances sensitivity to DDP in NSCLC cell.

Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Silencing ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Plasmids ; genetics ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptor, IGF Type 1 ; metabolism ; Transfection

OBJECTIVETo investigate the effect of Chinese herbs for nourishing yin and removing fire (NYRF) on gene expressions of estrogen receptor alpha (ER alpha), insulin-like growth factor-1 receptor (IGF-1R) and epithelial growth factor receptor (EGFR) in the epiphyseal growth plate of the female pubertal rats.

METHODSThe rats were randomly divided into the control group and the intervened group. Immunohistochemistry and realtime-PCR methods were used to measure the gene expression of ER alpha, IGF-1R and EGFR and their protein synthesis in epiphyseal growth plate.

RESULTSAfter being intervened with NYRF, the gene expressions of ER alpha and IGF-1R were down-regulated and their protein synthesis markedly reduced, while those of EGFR were unchanged.

CONCLUSIONNYRF can modulate the development and maturation of bone by regulating the expressions of ER alpha and IGF-1R in the epiphyseal growth plate.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Gene Expression ; drug effects ; Growth Plate ; drug effects ; metabolism ; Humans ; Protein Biosynthesis ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Receptor, IGF Type 1 ; genetics ; metabolism ; Yin-Yang

OBJECTIVETo explore the mechanism of Er'zhi Tiangui Granule (ETG) in improving the quality of oocyte.

METHODSNinety mice were randomly divided into 6 groups. The number of high-quality oocytes was comparatively observed in the 1st experimental group and the 1st control group; the embryonic cleavage rate was observed in the 2nd experimental group and the 2nd control group and the quantity of insulin-like growth factor-1R mRNA (IGF-1R mRNA) expression in ovarian granular cells was determined by using in situ hybridization in the 3rd experimental group and the 3rd control group.

RESULTSThe high-quality oocytes rate, the embryonic cleavage rate and the quantity of IGF-1R mRNA expression in the three paired groups was (78 +/- 8)% vs (71 +/- 5)%, (88 +/- 3)% vs (83 +/- 5)%, 0.4890 +/- 0.0454 vs 0.4439 +/- 0.0283, respectively. The difference between the experimental groups to the respective control groups was significant (all P < 0.05), and positive correlation was shown between the high-quality oocytes rate and the quantity of IGF-1R mRNA expression.

CONCLUSIONThe mechanism of ETG in improving the quality of oocyte may be related with the elevation of IGF-1R mRNA level in ovarian granular cells.

Animals ; Cleavage Stage, Ovum ; physiology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression ; Male ; Mice ; Oocytes ; drug effects ; physiology ; Ovary ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Receptor, IGF Type 1 ; biosynthesis ; genetics