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1.
Sci Rep ; 14(1): 4191, 2024 02 20.
Article in English | MEDLINE | ID: mdl-38378786

ABSTRACT

Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/ß in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes-PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Becaplermin/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Lung Neoplasms/pathology , Adenocarcinoma of Lung/pathology , Cell Transformation, Neoplastic/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Cell Line, Tumor
2.
Singapore medical journal ; : 157-160, 2016.
Article in English | WPRIM (Western Pacific) | ID: wpr-296458

ABSTRACT

<p><b>INTRODUCTION</b>C-X-C chemokine receptor type 7 (CXCR7) has recently been characterised as a novel receptor for the C-X-C motif chemokine 12 (CXCL12)/stromal cell-derived factor 1-alpha. CXCR7 has been thought to play an important role in the pathogenesis of chronic rhinosinusitis, angiogenesis and tumour metastasis. The present study aimed to examine the expression of CXCR7 in tissue samples of laryngeal cancer and maxillary sinus carcinoma to determine its role in the development of otorhinolaryngologic neoplasms.</p><p><b>METHODS</b>Samples of otorhinolaryngologic neoplasms were obtained from 17 patients with either nasal polyps (n = 7), laryngeal cancer (n = 5) or maxillary sinus carcinoma (n = 5), and who underwent surgical resection at West China Hospital of Sichuan University. Total RNA was isolated and CXCR7 mRNA expression was examined and quantified by relative real-time reverse transcription polymerase chain reaction. A one-way analysis of variance was performed using SPSS Statistics version 11.0 (SPSS Inc, Chicago, IL, USA) to compare the CXCR7 mRNA levels among the three groups of patients.</p><p><b>RESULTS</b>All samples tested positive for CXCR7 mRNA. The quantitative results showed that the CXCR7 mRNA levels were highest in laryngeal cancer and lowest in maxillary sinus carcinoma neoplasms, although there was no significant difference among the three samples.</p><p><b>CONCLUSION</b>CXCL12 and its receptor CXCR7 may contribute to eosinophilic inflammation in patients with chronic sinusitis and nasal polyps. Our results also suggest that CXCR7 may play a role in the progression, metastasis and angiogenesis of otorhinolaryngologic tumours.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Biomarkers, Tumor , Genetics , Carcinoma, Squamous Cell , Genetics , Metabolism , Pathology , Disease Progression , Gene Expression Regulation, Neoplastic , Otorhinolaryngologic Neoplasms , Genetics , Metabolism , Pathology , RNA, Neoplasm , Genetics , Real-Time Polymerase Chain Reaction , Receptors, CXCR , Genetics
3.
Biochem Biophys Res Commun ; 443(3): 802-7, 2014 Jan 17.
Article in English | MEDLINE | ID: mdl-24342610

ABSTRACT

MicroRNAs (miRNAs) are involved in controlling hepatocyte proliferation during liver regeneration. In this study, we established the miRNAs-expression patterns of primary hepatocytes in vitro under stimulation of epidermal growth factor (EGF), and found that microRNA-21 (miR-21) was appreciably up-regulated and peaked at 12h. In addition, we further presented evidences indicating that miR-21 promotes primary hepatocyte proliferation through in vitro transfecting with miR-21 mimics or inhibitor. We further demonstrated that phosphatidylinositol 3'-OH kinase (PI3K)/Akt signaling was altered accordingly, it is, by targeting phosphatase and tensin homologue deleted on chromosome 10, PI3K/Akt signaling is activated by miR-21 to accelerate hepatocyte rapid S-phase entry and proliferation in vitro.


Subject(s)
Hepatocytes/cytology , Hepatocytes/enzymology , MicroRNAs/metabolism , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Animals , Cell Cycle/genetics , Cell Proliferation , Cells, Cultured , Cyclin E/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Gene Expression Profiling , Genome/genetics , Liver Regeneration/genetics , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Up-Regulation/genetics
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-295541

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of dihydroartemisinin (DHA) on the BCR/ABL fusion gene in leukemia K562 cell.</p><p><b>METHODS</b>K562 cells were cultured in vitro. The rate of proliferation inhibition of cells treated with various concentrations of DHA were determined by using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) method. Expression of BCR/ABL fusion gene was analyzed by reverse transcription(RT-PCR) before and after DHA treatment. Apoptosis of K562 cells was detected by flow cytometry.</p><p><b>RESULTS</b>The growth of K562 cells was inhibited when the concentrations of DHA were 10-160 umol/L. With the added dose of DHA, the growth inhibition was remarkable, with the rate of inhibition risen from 52.76% to 94.65%. The expression of BCR/ABL fusion gene, as detected by RT-PCR after incubating the K562 cells with 20 umol/L DHA, measured as ΔCt = 4.45 ± 0.25 after 12 h and ΔCt = 5.23 ± 0.21 after 24 h, which was significantly lower compared with that of the control ( ΔCt = 4.23 ± 0.21, P < 0.05).</p><p><b>CONCLUSION</b>DHA can inhibit the proliferation of leukemia K562 cells and facilitate the induction of apoptosis by downregulating the expression of BCR/ABL fusion gene.</p>


Subject(s)
Humans , Artemisinins , Pharmacology , Fusion Proteins, bcr-abl , Genetics , Gene Expression , Genes, abl , K562 Cells , Leukemia , Genetics , Tumor Cells, Cultured
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-295536

ABSTRACT

<p><b>OBJECTIVE</b>To develop a rapid method for the detection of Down syndrome (DS) using dual-color competitive quantitative fluorescent polymerase chain reaction (DCC-QF-PCR), and to assess its feasibility for the prenatal diagnosis of Down syndrome.</p><p><b>METHODS</b>DNA was extracted from peripheral blood of 30 DS patients and 60 normal men, common primers for DSCR and USC2 genes and respective TaqMan probes were designed and synthesized. The results of DCC-QF-PCR were compared with those of QF-PCR which measured the ratio between DSCR and GAPDH. Forty-six amniotic fluid samples were assayed with DCC-QF-PCR. The results were compared with that of karyotyping. Monoclone fragments for DSCR and USC2 genes were obtained from direct cloning of PCR products. DCC-QF-PCR was carried out using different DNA ratios of DSCR and USC2 as the template. The dosage ratio between DSCR and USC2 was calculated.</p><p><b>RESULTS</b>The gene dosage ratio of the DS patients was 1.41-1.74, which was significantly higher than that of normal men (0.93-1.15). The dosage ratio range of DSCR and GAPDH by QF-PCR was comparatively greater than that of DSCR and USC2. Three samples were diagnosed as DS, which was in good agreement with that of karyotyping analysis. There was no significant difference between the gene dosage ratio from DCC-QF-PCR and that of predetermined (P>0.05).</p><p><b>CONCLUSION</b>DCC-QF-PCR is an accurate, rapid, and low cost method, which only requires tiny amount of sample and therefore has broad application in the genetic and prenatal diagnosis.</p>


Subject(s)
Humans , Down Syndrome , Diagnosis , Genetics , Fluorescent Dyes , Chemistry , Gene Dosage , Karyotyping , Methods , Polymerase Chain Reaction , Methods , Prenatal Diagnosis , Methods
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-273811

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression differences of minichromosome maintenance 2 (MCM2) mRNA and protein among colon adenocarcinoma, colon adenoma and normal mucosa, and among different clinicopathological types of adenomas.</p><p><b>METHODS</b>Fifty specimens, including 33 colonic adenomas, 12 colonic adenocarcinomas and 5 normal colonic mucosa were selected. Each specimen was divided into two parts, one for immunohistochemistry and the other for real-time RT-PCR. Expression differences of MCM2 mRNA among the colonic adenocarcinoma, adenoma and normal colonic mucosa were evaluated by REST-XL software.</p><p><b>RESULTS</b>The expression of MCM2 was observed in the basal third to half of the colonic crypts in normal mucosa, while throughout the epithelium in the colonic adenocarcinomas and adenomas. However, the expression of MCM2 mRNA in the adenocarcinomas was significantly higher than that in the adenomas(P=0.001). The MCM2 mRNA expression was elevated in the adenoma with villous type, in the conditions of high-grade dysplasia, larger size, sessile morphology and in patients of older ages, but the difference was not significant by REST-XL (P>0.05).</p><p><b>CONCLUSION</b>The difference of MCM2 expression between the adenoma and the adenocarcinoma indicates its potential value in the early diagnosis of colonic cancer.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Metabolism , Pathology , Adenoma , Metabolism , Pathology , Biomarkers, Tumor , Metabolism , Cell Cycle Proteins , Genetics , Metabolism , Colonic Neoplasms , Metabolism , Pathology , Minichromosome Maintenance Complex Component 2 , Nuclear Proteins , Genetics , Metabolism , RNA, Messenger
7.
Chinese Journal of Hematology ; (12): 661-665, 2006.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-328404

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of CYR61 and VEGF in extranodal nasal-type NK/T cell lymphoma and its significance.</p><p><b>METHODS</b>CYR61 mRNA and VEGF mRNA were detected by real-time fluorescence quantitative PCR method in 20 cases of extranodal nasal-type NK/T cell lymphoma. Expressions of CYR61 and VEGF were studied by immunohistochemistry in 40 cases of the tumor.</p><p><b>RESULTS</b>(1) Over-expression of CYR61 mRNA and VEGF mRNA was found in 19/20(95.0% ) and 15/20(75.0% ) cases, respectively. (2)Tumor cells expressing CYR61 protein and VEGF protein were detected in 38(95.0% ) and 25 (62. 5% ) of the 40 cases respectively, being no significant difference from the control. Co-expression of CYR61 and VEGF at both the mRNA and protein levels was 95.0% and 65.0% , respectively. Over-expression of CYR61 and VEGF at both mRNA and protein levels was found in 8 of the 40 cases. (3) The prognosis of the patients over-expressing CYR61 and VEGF was worse.</p><p><b>CONCLUSION</b>In extranodal nasal-type NK/T cell lymphoma, the expression level of CYR61 and VEGF was changed and it may be of prognostic implication of</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Cysteine-Rich Protein 61 , Immediate-Early Proteins , Genetics , Intercellular Signaling Peptides and Proteins , Genetics , Killer Cells, Natural , Lymphoma, T-Cell , Metabolism , Pathology , Nose Neoplasms , Metabolism , Pathology , Polymerase Chain Reaction , RNA, Messenger , Vascular Endothelial Growth Factor A , Genetics
8.
Chinese Journal of Stomatology ; (12): 266-270, 2005.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-273240

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mutational characteristics of PAX9 gene in Chinese patients with congenital oligodontia and thus to provide a molecular basis for studying the pathogenesis of oligodontia.</p><p><b>METHODS</b>Thirteen individuals with oligodontia and 9 healthy individuals, from 4 unrelated autosomal dominant families, and 16 sporadic patients with hypodontia in China, as well as 196 healthy control individuals (without oligodontia or hypodontia) were screened. Congenital absence of teeth was confirmed by panoramic X-ray analysis. Mutations of PAX9 gene were detected using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. After the finding of abnormal SSCP bands, analysis was carried out with DNA sequencing.</p><p><b>RESULTS</b>PCR-SSCP detected SSCP bands alteration in exon2 of PAX9 gene in two unrelated families. Sequencing of PAX9 gene revealed a novel frameshift mutation (109InsG) and a novel missense mutation (C139T). All the affected members of each family were heterozygous for the mutations. In sporadic patients and the other two families, no similar sequence changes in PAX9 gene were found.</p><p><b>CONCLUSIONS</b>The results extend the spectrum of mutations in PAX9 gene associated with oligodontia. The novel mutations will play an important role in gene diagnosis of oligodontia.</p>


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Genetics , Frameshift Mutation , Mutation, Missense , PAX9 Transcription Factor , Genetics , Pedigree , Tooth Loss , Genetics
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