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1.
Bioengineered ; 13(5): 12807-12822, 2022 05.
Article in English | MEDLINE | ID: mdl-35611880

ABSTRACT

Osteonecrosis of the femoral head (ONFH) caused by steroids is a severe orthopedic disorder resulting from the use of high-dose steroid drugs, characterized by structural changes in the bone, joint dysfunction, and femoral head collapse. CircRNAs and miRNAs have increasingly been suggested to play pivotal roles in osteogenic differentiation and osteogenesis. Significant upregulation of circ_0058792 was observed in patients with steroid-induced ONFH. Bioinformatic analysis showed that circ_0058792 might act as a sponge for miR-181a-5p. This study further investigated the mechanisms underlying the role of circ_0058792 and miR-181a-5p in osteogenic differentiation in methylprednisolone-induced ONFH rats and MC3T3-E1 cells. The results showed a notable decrease in the serum of miR-181a-5p in methylprednisolone-induced ONFH rats. Silencing of circ_0058792 using siRNAs and overexpression of miR-181a-5p significantly increased alkaline phosphatase activity and matrix mineralization capacity. Additionally, markers for osteogenic differentiation were significantly upregulated in miR-181a-5p-transfected cells. However, overexpression of circ_0058792 and the addition of the miR-181a-5p inhibitor reversed this increase. Smad7 was identified to be miR-181a-5p's direct target and circ_0058792 was confirmed to be miR-181a-5p's competing endogenous RNA (ceRNA). Upregulation of miR-181a-5p promotes phosphorylation of Smad2 and Smad3. Furthermore, circ_0058792 and miR-181a-5p had opposing effects on Smad7 expression. Collectively, these findings indicate that circ_0058792 regulates osteogenic differentiation by sponging miR-181a-5p via the TGF-ß/Smad7 pathway. These findings elucidated the functions of circ_0058792 and miR-181a-5p in the regulation of steroid-induced ONFH. Our findings also indicated that circ_0058792 and miR-181a-5p are possible diagnostic markers and therapeutic targets for treating steroid-induced ONFH.


Subject(s)
Femur Head Necrosis , MicroRNAs , RNA, Circular , Smad7 Protein , Animals , Cell Differentiation/genetics , Femur Head/metabolism , Femur Head Necrosis/chemically induced , Femur Head Necrosis/genetics , Femur Head Necrosis/metabolism , Humans , Methylprednisolone/toxicity , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Osteogenesis/genetics , RNA, Circular/genetics , Rats , Smad7 Protein/genetics , Smad7 Protein/metabolism , Steroids/adverse effects
2.
FEBS Open Bio ; 9(12): 2052-2062, 2019 12.
Article in English | MEDLINE | ID: mdl-31605569

ABSTRACT

Tumor-derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high-throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real-time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA-miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Extracellular Vesicles/genetics , RNA, Circular/genetics , Adenocarcinoma/blood , Adenocarcinoma/genetics , Adult , Carcinoma, Pancreatic Ductal/blood , Cell Line, Tumor , Computational Biology/methods , Female , Gene Expression Profiling/methods , Humans , Male , MicroRNAs/genetics , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/genetics , RNA, Circular/analysis , RNA, Circular/blood , Real-Time Polymerase Chain Reaction/methods , Transcriptome/genetics , Pancreatic Neoplasms
3.
Pathol Oncol Res ; 21(3): 719-25, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25613817

ABSTRACT

Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and adenoma vs. CRC, were identified using the Wilcoxon test method in R respectively. The interactive network of DEGs was constructed to select the significant modules using the Pearson's correlation. Meanwhile, transcriptional network of DEGs was also constructed using the g: Profiler. Totally, 2,741 DEGs in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs. CRC were identified. Moreover, function analysis of DEGs in each group showed FcR-mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in module 6, and Jak-STAT signaling pathway in module 19 were also enriched. Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT, SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development. Therapy targeting on the functions of these key genes might provide novel perspective for CRC treatment.


Subject(s)
Adenoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Transcription Factors/genetics , Colon/metabolism , Computational Biology , Humans , Rectum/metabolism
4.
J Int Med Res ; 42(4): 993-1001, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24925584

ABSTRACT

OBJECTIVE: To compare the treatment effects of Novolin® 30R(a), versus Lantus(®a) combined with acarbose (Glucobay®), in elderly patients with type 2 diabetes mellitus. METHODS: Patients (aged > 60 years) with type 2 diabetes mellitus were randomized to receive either Novolin® 30R(a) (initial dose 0.5 IU/kg) or Lantus(®a) (initial dose 0.2 IU/kg) combined with 50 mg acarbose. After a 32-week treatment period, the following parameters were measured: blood glucose control; blood lipid levels; body mass index; proportion of patients achieving a glycosylated haemoglobin (HbA1c) level <7.5%; rate of hypoglycaemic events; change in fasting blood glucose levels from baseline in patients stratified according to their baseline HbA1c level. RESULTS: A total of 188 patients were enrolled in the study. After 32 weeks' treatment, compared with baseline levels, there were significant reductions in FBG, 2 h-postprandial blood glucose during an oral glucose tolerance test, HbA1c, total cholesterol, triglycerides and low-density lipoprotein cholesterol values in both groups. Although there were fewer hypoglycaemic events in the Lantus® combined with Glucobay® group compared with the Novolin® 30R group, the difference was not significant. CONCLUSION: Novolin® 30R and Lantus® combined with acarbose both had beneficial effects on blood glucose control and blood lipid levels in elderly patients with type 2 diabetes mellitus.


Subject(s)
Acarbose/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin Glargine/therapeutic use , Insulin/therapeutic use , Aged , Blood Glucose/drug effects , Body Mass Index , Drug Therapy, Combination , Female , Glycated Hemoglobin/metabolism , Humans , Lipids/blood , Male , Prospective Studies
5.
Cell Biochem Biophys ; 61(2): 377-82, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21830127

ABSTRACT

Thyroid stimulating hormone receptor (TSHR) is thought to play a critical role in the pathogenesis of certain thyroid diseases, including Graves' disease (GD), multinodular thyroid goiter (MTG), and Hashimoto's thyroiditis (HT). In order to understand whether single nucleotide polymorphisms in the TSHR gene contribute to thyroid diseases, we have conducted a case-control study in which, we examined 8 TSHR gene single-nucleotide polymorphisms in introns 1, 4, 5, 6 and exons 7 and 8, respectively, among patients with thyroid diseases. These included one family with GD (3 patients and 9 healthy members); 60 patients with familiar thyroid diseases (30 with GD, 20 with MTG, and 10 with HT patients), 48 sporadic patients with GD and 96 healthy control individuals. Direct sequencing of all 10 exons and part of introns of TSHR gene, in these patients as well as healthy controls revealed eight polymorphisms. A novel polymorphism in exon 8 AGA(Arg) → CGA(Arg). However, there were no significant differences between patients and controls in the incidence of these polymorphisms. These results suggest that the polymorphisms (polymorphism in intron 1 at 81 bp upstream of exon 2; polymorphism in intron 4 at 135 bp upstream of exon 5; polymorphism in intron 4 at 365 bp upstream of exon 5; polymorphism in intron 5 at 69 bp upstream of exon 6; means polymorphism in intron 6 at 13 bp downstream of exon 6; polymorphism in intron 6 at 187 bp upstream of exon 7; E7+16: polymorphism in 16 bp of exon 7; polymorphism in 40 bp of exon 8) of the TSHR gene may not contribute to the pathogenesis of thyroid diseases.


Subject(s)
Receptors, Thyrotropin/genetics , Thyroid Diseases/genetics , Case-Control Studies , Exons/genetics , Female , Genotype , Humans , Introns/genetics , Male , Middle Aged , Pedigree , Polymorphism, Single Nucleotide/genetics
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(1): 64-7, 2010 Jan.
Article in Chinese | MEDLINE | ID: mdl-20099166

ABSTRACT

OBJECTIVE: To construct the plasmid expression vector pSIH1-H1-copGFP for RNA interference against vascular endothelial growth factor C (VEGF-C) and to evaluate its effect on the expression of VEGF-C mRNA in gastric cancer cells after transfection. METHODS: Three siRNAs of genome sequence of VEGF-C gene were retrieved from GenBank and one negative chain was used as control. Four siRNAs were cloned into plasmid pSIH1-H1-copGFP,which were then transfected into gastric cancer cells (SGC7901). The expression of VEGF-C mRNA was analyzed by RT-PCR. RESULTS: The recombinant plasmid of pSIH1-H1-copGFP specific for VEGF-C was confirmed by gene sequencing analysis. The target sequence obtained was completely consistent with the design. Transfection efficiency of the three siRNAs ranged from 60% to 70%. After transfection, the expression of VEGF-C mRNA in SGC7901 cells was significantly inhibited. Inhibition rates of VEGF-C mRNA expression were 35.4%, 33.8% and 81.5% in the three siRNA plasmid vectors, respectively. CONCLUSION: The siRNA expression plasmid vector against VEGF-C mRNA is successfully constructed, and RNAi may be a useful technique to inhibit the lymphangiogenesis of gastric cancer.


Subject(s)
RNA Interference , RNA, Small Interfering , Stomach Neoplasms/genetics , Vascular Endothelial Growth Factor C/genetics , Cell Line, Tumor , Genetic Vectors , Humans , Plasmids , Transfection
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