Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 89
Filtrar
1.
Onco Targets Ther ; 12: 9827-9848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819482

RESUMO

Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinico-pathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

2.
Orthop Surg ; 11(6): 1142-1148, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31724289

RESUMO

OBJECTIVE: To explore the difference in pelvic tilt and hip joint parameters with developmental dysplasia of the hip (DDH) comparing the anteroposterior (AP) pelvic radiographs taken in supine and standing positions. METHODS: A prospective study of DDH patients undergoing Bernese periacetabular osteotomy (PAO) was conducted. AP pelvic radiographs were taken in supine and standing positions before surgery The pelvic tilt and hip joint parameters from the two radiographs were compared. Contrast parameters included the distance between the pubic symphysis to sacrococcygeal distance (PSSC), lateral center-edge angle (LCEA), Tönnis angle (TA), and angle of sharp (SA). RESULTS: A total of 110 young DDH patients were enrolled, including 32 men and 78 women, aged 18-49 years. The male PSSC was 45.63 ± 13.69 mm in supine position and 36.91 ± 12.33 mm in standing position (P < 0.05). The female PSSC was 56.76 ± 13.54 mm in supine position and 48.62 ± 15.44 mm in standing position (P < 0.05). In this study, LCEA <20° in AP pelvic radiographs in the supine position was found in 52 men and 135 women. For male patients, in supine position and standing position, LCEA were 5.51° ± 11.88° and 4.45° ± 12.22°, respectively (P < 0.05); TA were 20.20° ± 9.63° and 21.30° ± 9.97°, respectively (P < 0.05), and SA comparison showed no significant differences. For female patients, in supine position and standing position, LCEA were 3.07° ± 12.07° and 1.69° ± 12.11°, respectively (P < 0.05), TA were 22.62° ± 9.31° and 23.82° ± 9.45°, respectively (P < 0.05), and SA were 48.01° ± 4.68° and 48.49° ± 4.74°, respectively (P < 0.05). CONCLUSION: Compared with the supine position, the young DDH patients have pelvic tilt backward and a decrease in hip coverage in the standing position.

3.
J Cancer ; 10(22): 5339-5354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632479

RESUMO

Gastric cancer (GC) threatens human health worldwide and we performed this meta-analysis to evaluate the clinical value of Ki-67/MKI67 in patients with GC. The combined hazard ratio (HR), odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the relationships of Ki-67/MKI67 expression with prognoses and clinicopathological characteristics. Genes co-expressed with MKI67 were collected for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses. In total, 53 studies with 7078 patients were included in this study. The pooled HRs indicated that an elevated expression of Ki-67/MKI67 predicted an unfavorable overall survival (HR: 1.54, 95% CI: 1.33-1.78, P<0.0001) and disease-free survival (HR: 2.28, 95% CI: 1.43-3.64, P<0.0001) in GC patients. Additionally, in patients with advanced GC, a high Ki-67/MKI67 expression was also significantly connected with OS (HR: 1.37, 95% CI: 1.18-1.60, P<0.0001). The combined ORs showed that Ki-67/MKI67 expression was related to TNM stage (stage III/IV versus stage I/II: OR=1.93, 95% CI=1.34-2.78, P<0.0001), tumor differentiation (poor versus well/moderate: OR=1.94, 95% CI=1.32-2.85, P=0.001), lymph node metastasis (yes versus no: OR=1.67, 95% CI=1.23-2.25, P=0.001), distant metastasis (yes versus no: OR=1.67, 95% CI=1.24-2.26, P=0.001) and tumor invasion depth (T3/T4 versus Tis/T1/T2: OR=1.98, 95% CI=1.60-2.44, P<0.0001). The results of GO, KEGG pathway and PPI network analyses indicated that Ki-67/MKI67 may be involved in the development of GC via influencing P53 signaling pathway. Ki-67/MKI67 could be a potential indicator to predict the prognosis of patients with GC and identify high-risk cases. Detecting Ki-67/MKI67 expression in clinic may be helpful in optimizing individual treatment and further improving the survival expectancy of patients with GC.

4.
Cell Death Dis ; 10(9): 658, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506425

RESUMO

Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as "miRNA sponges" in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. Eighteen hubgenes (SMARCD1, CBX1, HCFC1, RBM12B, RCC2, NUP205, ECT2, PRIM2, RBM28, COPS7B, PRRC2A, GPR107, ANKRD52, TUBA1B, ATXN7L3, FUS, MCM8 and RACGAP1) associated with clinical outcomes of HCC patients were then identified. These findings showed that the crosstalk between hsa_circ_0088364 and hsa_circ_0090049 and their competing mRNAs may play important roles in HCC, providing interesting clues into the potential of circRNAs as therapeutic targets of NC in HCC.

5.
Cancer Cell Int ; 19: 167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285693

RESUMO

Background/aims: Studies have shown that miR-146a-5p was differentially expressed in diverse cancers, but the associations between miR-146a-5p expression and prognosis across multiple types of cancer as well its potential targets and downstream pathways have not been comprehensively analyzed. In this study, we performed the first meta-analysis of the prognostic value of miR-146a-5p expression in diverse malignancies and explored prospective targets of miR-146a-5p and related signaling pathways. Methods: A thorough search for articles related to miR-146a-5p was performed, and RNA-seq data from The Cancer Genome Atlas (TCGA) and microarray data from gene expression omnibus profiles were used to collect information about the prognostic value of miR-146a-5p. A comprehensive meta-analysis was conducted. Twelve platforms in miRWalk 2.0 were applied to predict targets of miR-146a-5p. TCGA RNA-seq data were used to validate the inverse relationships between miR-146a-5p and its likely targets. Subsequently, gene ontology and pathway analyses were conducted using Funrich version 3.1.3. Potential protein-protein interaction (PPI) networks were constructed. Potential target genes of miR-146a-5p in lung cancer were validated by RT-qPCR. Results: We included 10 articles in the meta-analysis. In a pooled analysis, the high miR-146a-5p expression group showed a better overall survival in solid cancers, particularly in reproductive system cancers and digestive system cancers. A total of 120 predicted target genes were included in a bioinformatics analysis. Five pathways involving phospholipase C (PLC) and aquaporins (AQPs) were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, the PPI network displayed the related signaling pathways and interactions among proteins. AQP1 and FYN were validated by RT-qPCR to be potential targets of miR-146a-5p in lung cancer. Conclusion: There is a close link between high miR-146a-5p expression and better overall survival in 21 types of solid cancer, especially in reproductive system and digestive system cancers. Furthermore, miR-146a-5p could inhibit diverse malignancies by modulating pathways linked to PLC or AQPs. In summary, miR-146a-5p is a potential prognostic biomarker and therapeutic target for various cancers.

6.
J Orthop Surg (Hong Kong) ; 27(2): 2309499019854039, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204578

RESUMO

BACKGROUND: The purpose of this study was to assess the influence of developmental dysplasia of the hip (DDH) on patella alignment. METHODS: The radiographic data of all the patients who met the inclusion criteria from January 2015 to July 2017 were reviewed, including the quadriceps angle (QA), patellar lateral tilt (PTA), sulcus angle (SA), lateral shift of patella (LSP), and lower limbs alignment. The patients were divided into three groups in accordance with lateral center-edge angle (LCE) and femoral neck torsion angle (FNTA): group A (LCE > 25° and FNTA < 40°), group B (LCE < 20° and FNTA < 40°), and group C (LCE < 20° and FNTA > 40°). RESULTS: One hundred thirty-eight patients with 230 hips (115 females and 23 males) were recruited with an average age of 22 years. There were significant differences between group A and group C as well as group B and group C in QA, SA, PTA, LSP, and lower limbs alignment (p < 0.01). There were no differences in SA, PTA, LSP, and lower limbs alignment (p >0.05) and significant differences in QA (p < 0.01) between group B and group C. The "Pearson's" correlation analysis of the data in total of group B and group C showed that FNTA and LCE and QA and LCE were negatively correlated, whereas FNTA and QA, PTA, SA, and lower limbs alignment as well as SA, PTA, and lower limbs alignment were positively correlated. CONCLUSION: Patients with DDH not only have hip joint change, but also have the patella alignment abnormality, which may lead to patella instability. In the clinic, we should pay attention to the hip development of the patella instability patients for excluding DDH. Level of Evidence: Prognostic level III.

7.
Cancer Manag Res ; 11: 4825-4837, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213904

RESUMO

Background: MicroRNAs (miRNAs) could modulate gene expression at the posttranscriptional level by promoting mRNA degradation or blocking mRNA translation, thus affecting the occurrence and development of cancer. Methods: In this work, qRT-PCR was conducted to detect the expression of miR-193a-3p and CCND1. The ability of cell proliferation was evaluated via CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Bioinformatic techniques were employed to research the regulatory relationship between miR-193a-3p and target genes. The relationship between miR-193a-3p and CCND1 was verified via dual-luciferase reporter assays. Results: MiR-193a-3p expression in pancreatic ductal adenocarcinoma (PDAC) tissue was significantly lower than in non-cancerous tissue. After overexpressing miR-193a-3p in PDAC cells, their multiplication ability was significantly inhibited, apoptosis was accelerated, and the cell cycle was blocked in the G1 and G2/M phases. CCND1 was confirmed to have a targeted relationship with miR-193a-3p. Moreover, CCND1 expression was significantly lower in PDAC cells with an overexpression of miR-193a-3p. Conclusions: MiR-193a-3p targeted CCND1 to suppress tumor growth in PDAC cells. MiR-193a-3p may function as a tumor inhibitor in PDAC development, which could offer a promising therapeutic and prognostic strategy for PDAC treatment.

8.
Oncol Rep ; 41(4): 2194-2208, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816530

RESUMO

MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM­associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa­miR­196a, hsa­miR­10b, hsa­miR­196b, hsa­miR­18b, hsa­miR­542­3p, hsa­miR­129­3p, hsa­miR­1224­5p, hsa­miR­876­3p and hsa­miR­770­5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer­associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin­dependent protein kinase type II subunit Gamma (CAMK2G), platelet­derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin­dependent kinase 6 (CDK6), calcium/calmodulin­dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma­associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W­13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA­based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Descoberta de Drogas/métodos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , MicroRNAs/metabolismo , Androstadienos/química , Androstadienos/farmacologia , Androstadienos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Biologia Computacional , Gefitinibe/química , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular/métodos , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Transcriptoma/genética
9.
Case Rep Gastroenterol ; 13(1): 17-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792619

RESUMO

It is rare that colon carcinoma and mantle cell lymphoma (MCL) occur one after another in intestines. We found two malignancies of sigmoid carcinoma and MCL in a single patient, who had initially been diagnosed with sigmoid carcinoma and treated with radical resection in our hospital. Good postoperative recovery was reported without recurrence signs, which lasted for 7 years and 5 months until polyps of sigmoid colon were found by colonoscopy. Biopsy and immunohistochemistry revealed MCL, but the patient refused treatment. One year later, MCL was diagnosed again in the transverse colon. The patient is currently under observation and has not received treatment for MCL.

10.
Exp Ther Med ; 17(2): 1351-1359, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30680013

RESUMO

The aim of the current study was to investigate the construction of the bone bridge and tibial plateau under arthroscopy during meniscal allograft transplantation, in order to simplify and enhance the accuracy of bone bridge fixation intraoperatively. A traction line passed through the attachment of the anterior and posterior horns of the superior meniscus to the bone bridge was used to pull the bone bridge into the knee joint cavity and fix the anteroposterior horns of the meniscus. At the junction of the body of the meniscus and the posterior and anterior horns of the meniscus, a traction line was created at the anterior and posterior 1/3 of the meniscus to pull and fix the meniscus. Under the arthroscope, the aiming device was placed on the tibial plateau. The direction and width of the guide plate were identical to those of the bone trough of the tibial plateau. The bone tunnel was made using the guide needle and a 9-mm hollow drill, the piston rod was inserted, and the arch-shaped bone knife was inserted along with the piston rod to construct the 9-mm bone trough of the tibial plateau. The periphery of the meniscus was sutured to the joint capsule. These surgical techniques and instruments could standardize meniscal graft transplantation and avoid the incidence of surgical errors caused by mismatched size and shape of the bone bridge and bone trough. This would make the surgery more convenient, safe and accurate. The four-point fixation of the tibial plateau contributed to preventing the reversal of the meniscus during transplantation, and partially reconstructed the coronary ligament of the meniscal tibia, which probably enhanced the stability of the meniscus and minimized the risk of extrusion of the meniscal allograft. The bone bridge and bone trough of the tibial plateau were properly constructed under arthroscopy. Dynamic monitoring of surgical indications, explicit preoperative preparation and standardized surgical procedures could achieve high efficacy and excellent fixation effect during meniscal graft transplantation. The four-point fixation of the tibial plateau maintains and enhances the stability of the meniscal allograft, reduces the risk of meniscal extrusion and ensures the postoperative recovery of meniscal function.

11.
Int Orthop ; 43(3): 573-577, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29911277

RESUMO

AIM: To investigate the incidence, risk factors, and the last follow-up recovery status of sciatic and femoral nerve injury among patients who received Bernese peri-acetabular osteotomy (PAO). PATIENTS AND METHODS: The clinical file of 643 consecutive patients who received PAO from June 2012 to June 2016 was retrospectively reviewed. The number of nerve injury patients was calculated and the causes of injury were recorded. RESULTS: The sciatic or femoral nerve injury occurred in eight patients (1.24%), including four sciatic nerve injuries and four femoral nerve injuries. The reasons for sciatic nerve injury included one direct sciatic nerve injury happened at the time when deep osteotomy penetrated the posterior column to cut the nerve trunk at the area where the nerve runs through out of the greater sciatic foramen during quadrilateral bone osteotomy. The other two direct sciatic nerve injuries occurred at the inside pelvis by long drill bit or Kirschner wire drilling before the transverse screw fixation. No direct injury reasons could be found for the remaining five patients with one partial sciatic nerve injury and four femoral nerve palsies. The three patients with direct sciatic nerve injuries were partly recovered at the last follow-up. Full recovery was found in one sciatic nerve injury and four femoral nerve injury patients. CONCLUSION: The sciatic nerve can be injured directly or indirectly during PAO. It is of great importance to understand the risk factors and the precautionary measures of nerve injuries during PAO.

12.
Pathol Res Pract ; 215(3): 414-426, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30455130

RESUMO

Malignant tumors of the digestive tract include esophageal, gastric, and colorectal carcinomas, which all have high global mortality rates. A clinical role for small nuclear RNA (snRNA), a type of small non-coding RNA, has not yet been documented for digestive tract pan-adenocarcinomas. Therefore, the aim of the study was to identify differentially expressed snRNAs and to explore their prognostic implications in pan-adenocarcinomas from the esophagus, stomach, colon, and rectum. The pan-carcinoma RNA-sequencing data of four types of digestive tract cancers with 1, 102 cases obtained from The Cancer Genome Atlas (TCGA) project were analyzed and the differentially expressed snRNAs were evaluated using the edgeR package. The prognostic value of each of the selected snRNAs was determined by univariate and multivariate Cox regression analyses. All the digestive tract pan-adenocarcinomas showed differential expression of three snRNAs: the up-regulated RNU1-106 P and RNU6-850 P and the down-regulated RNU6-529 P. Interestingly, RNU6-101 P appeared to be a risk factor for esophageal adenocarcinoma (ESAD) and RNVU1-4 was potentially a protective factor for stomach adenocarcinoma (STAD) survival. This consistent finding of differential expression of all three snRNAs in all four types of digestive system cancers suggests potential roles for these snRNAs in the tumorigenesis of digestive system cancers. RNU6-101 P could play a pivotal role in the progression of ESAD and RNVU1-4 could perform a protective role in STAD. However, since the current findings were based on RNA-sequencing data mining, more studies are needed for verification.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias do Sistema Digestório/genética , RNA Nuclear Pequeno/análise , Adenocarcinoma/mortalidade , Neoplasias do Sistema Digestório/mortalidade , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sequência de RNA
13.
Int J Oncol ; 54(2): 600-626, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30570107

RESUMO

Autophagy has been reported to be involved in the occurrence and development of pancreatic cancer. However, the mechanism of autophagy­associated non­coding RNAs (ncRNAs) in pancreatic cancer remains largely unknown. In the present study, microarrays were used to detect differential expression of mRNAs, microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs) post autophagy suppression by chloroquine diphosphate in PANC­1 cells. Collectively, 3,966 mRNAs, 3,184 lncRNAs and 9,420 circRNAs were differentially expressed. Additionally, only two miRNAs (hsa­miR­663a­5p and hsa­miR­154­3p) were underexpressed in the PANC­1 cells in the autophagy­suppression group. Furthermore, miR­663a­5p with 9 circRNAs, 8 lncRNAs and 46 genes could form a prospective ceRNA network associated with autophagy in pancreatic cancer cells. In addition, another ceRNA network containing miR­154­3p, 5 circRNAs, 2 lncRNAs and 11 genes was also constructed. The potential multiple ceRNA, miRNA and mRNA associations may serve pivotal roles in the autophagy of pancreatic cancer cells, which lays the theoretical foundation for subsequent investigations on pancreatic cancer.


Assuntos
Autofagia/efeitos dos fármacos , Cloroquina/análogos & derivados , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , RNA Neoplásico/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Cloroquina/farmacologia , Feminino , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , RNA/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo
14.
Cell Physiol Biochem ; 50(3): 823-840, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355917

RESUMO

BACKGROUND/AIMS: Accumulating evidence strongly suggests that microRNAs (miRNAs) modulate the expression of known tumor suppressor genes and oncogenes. In the present study, we found that the proliferation and invasion ability of pancreatic ductal adenocarcinoma (PDAC) cells were significantly suppressed by the overexpression of miR-23b-3p. In addition, there are miR-23b-3p binding sites in annexin A2 (ANXA2). Here, we investigated whether miR-23b-3p had an impact on the progression and metastasis of PDAC by targeting ANXA2. METHODS: Cell proliferation, migration, and invasion, and cell cycle assays were performed to explore the effect of miR-23b-3p on various malignant phenotypes of pancreatic cancer cells. The size of tumors was observed following miR-23b-3p overexpression in an in vivo chick chorioallantoic membrane assay. Dual-luciferase reporter, quantitative real-time PCR, western blot, and immunohistochemical analyses were used to validate the relationship between miR-23b-3p and ANXA2 in vitro. RESULTS: We observed that miR-23b-3p could bind specifically to the 3' untranslated region of ANXA2 and inhibit its expression. MiR-23b-3p overexpression downregulated the expression of ANXA2 mRNA in PDAC cells and limited the size of tumors or even prevented tumor formation. In addition, there was a negative correlation between miR-23b-3p expression and ANXA2 protein expression in clinical specimens. CONCLUSION: MiR-23b-3p inhibits the development and progression of PDAC by regulating ANXA2 directly.


Assuntos
Anexina A2/metabolismo , Carcinoma Ductal Pancreático/patologia , MicroRNAs/metabolismo , Neoplasias Pancreáticas/patologia , Regiões 3' não Traduzidas , Adulto , Animais , Anexina A2/genética , Antagomirs/metabolismo , Sequência de Bases , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/patologia , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Neoplasias Pancreáticas/metabolismo , Alinhamento de Sequência
15.
J Transl Med ; 16(1): 220, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30092792

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). METHODS: A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC. RESULTS: Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA-miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein-protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis. CONCLUSIONS: Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroRNAs/genética , RNA/genética , Algoritmos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sequência de Bases , Bases de Dados como Assunto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Mapas de Interação de Proteínas/genética , RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 32(7): 854-859, 2018 07 15.
Artigo em Chinês | MEDLINE | ID: mdl-30129308

RESUMO

During the past decades, the field of hip preservation in China has achieved great improvements. Theoretically, the blood supply of the femoral head and the acetabulum along with the mechanism of early-stage hip osteoarthritis has been gradually cleared. The knowledge and application of the periacetabular osteotomy, surgical hip dislocation, and hip arthroscopy has been vigorously promoted. Improved understanding of the mechanism, pathology, and prevention protocols of the secondary hip dysplasia have been obtained, despite the fact that lack of awareness of some mechanism and detail, for example, hip instability or borderline dysplasia, etc. On the basis of summing up those clinical progress, this article further elaborated the historical development of hip preservation through the review of several traditional treatment, and made objective assessment about the follow-up, evaluation, minimally invasive surgery, and individualized treatment newly reported.


Assuntos
Luxação Congênita de Quadril , Osteotomia , Acetábulo/cirurgia , Adulto , China , Luxação Congênita de Quadril/cirurgia , Humanos , Osteoartrite do Quadril , Resultado do Tratamento
17.
Pathol Res Pract ; 214(9): 1260-1272, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30017333

RESUMO

Urothelial cancer associated 1 (UCA1) was upregulated in hepatocellular carcinoma (HCC) tissues and cell lines, and the expression of UCA1 was associated with several clinical features and malignant behaviours in HCC. However, none of these findings completely interpreted the role of UCA1 in HCC. We conducted this investigation to validate the expression of UCA1 and its relationship with Tumor Node Metastasis (TNM) stage in 41 HCC tissues and their paired noncancerous adjacent tissues by real-time qPCR. Furthermore, we also explored the biological functions of UCA1 in vitro with HCC cell lines. Most importantly, we conducted a comprehensive meta-analysis and bioinformatics investigation based on peer-reviewed literature and in silico approaches to further summarise the clinical value and functions of UCA1 in HCC. UCA1 expression was remarkably upregulated in HCC tissues, and its expression was profoundly higher in advanced stages than in early stages. Reducing the expression levels of UCA1 suppressed the proliferation and induced apoptosis of HCC cells. Furthermore, the present meta-analysis validated that up-regulated UCA1 was closely related to larger tumour size and advanced TNM stages, and the overexpression of UCA1 was significantly correlated with a shorter OS. Additionally, according to GO analysis, the target genes were found concentrated in the following biological processes: extracellular matrix organisation, cilium assembly and cilium morphogenesis. KEGG pathway analysis showed that the UCA1-related genes were significantly enriched in the following pathways: hippo signalling pathway, bile secretion and gastric acid secretion. This evidence hinted that UCA1 could play an indispensable proliferation-related key role in HCC via the hippo signalling pathway. However, the exact molecular mechanism needs to be verified with future functional experiments.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade
18.
Cell Physiol Biochem ; 48(3): 905-918, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30036873

RESUMO

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). METHODS: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. RESULTS: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3'-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. CONCLUSIONS: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Apoptose , Área Sob a Curva , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Factuais , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/química , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Curva ROC , Alinhamento de Sequência , Fatores Estimuladores Upstream/química , Fatores Estimuladores Upstream/genética , Fatores Estimuladores Upstream/metabolismo
19.
Cell Physiol Biochem ; 47(6): 2216-2232, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975928

RESUMO

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) remains a difficult problem that significantly affects the survival of the afflicted patients. Accumulating evidence has demonstrated the functions of long non-coding RNA (lncRNA) in HCC. In the present study, we aimed to explore the potential roles of PVT1 in the tumorigenesis and progression of HCC. METHODS: In this study, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was applied to detect the differences between PVT1 expression in HCC tissues and cell lines. Then, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were searched to confirm the relationship between PVT1 expression and HCC. Moreover, a meta-analysis comprising TCGA, GEO, and RT-qPCR was applied to estimate the expression of PVT1 in HCC. Then, cell proliferation was evaluated in vitro. A chicken chorioallantoic membrane (CAM) model of HCC was constructed to measure the effect on tumorigenicity in vivo. To further explore the sponge microRNA (miRNA) of PVT1 in HCC, we used TCGA, GEO, a gene microarray, and target prediction algorithms. TCGA and GEO and the gene microarray were used to select the differentially expressed miRNAs, and the different target prediction algorithms were applied to predict the target miRNAs of PVT1. RESULTS: We found that PVT1 was markedly overexpressed in HCC tissue than in normal liver tissues based on both RT-qPCR and data from TCGA, and the overexpression of PVT1 was closely related to the gender and race of the patient as well as to higher HCC tumor grades. Also, a meta-analysis of 840 cases from multiple sources (TCGA, GEO and the results of our in-house RT-qPCR) showed that PVT1 gained moderate value in discriminating HCC patients from normal controls, confirming the results of RT-qPCR. Additionally, the upregulation of PVT1 could promote HCC cell proliferation in vitro and vivo. Based on the competing endogenous RNA (ceRNA) theory, the PVT1/miR-424-5p/INCENP axis was finally selected for further research. The in silico prediction revealed that there were complementary sequences between PVT1 and miR-424-5p as well as between miR-424-5p and INCENP. Furthermore, a negative correlation trend was found between miR-424-5p and PVT1 based on RT-qPCR, whereas a positive correlation trend was found between PVT1 and INCENP based on data from TCGA. Also, INCENP small interfering RNA (siRNA) could significantly inhibit cell proliferation and viability. CONCLUSIONS: We hypothesized that PVT1 could affect the biological function of HCC cells via targeting miR-424-5p and regulating INCENP. Focusing on the new insight of the PVT1/miR-424-5p/INCENP axis, this study provides a novel perspective for HCC therapeutic strategies.


Assuntos
Carcinoma Hepatocelular , Proteínas Cromossômicas não Histona , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , RNA Longo não Codificante , RNA Neoplásico , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo
20.
Cell Physiol Biochem ; 48(2): 475-490, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016783

RESUMO

BACKGROUND/AIMS: Left- and right-sided colon cancers are considered to be two different diseases and have altered outcomes. However, specific molecules to predict the prognosis of left- and right-sided colon cancers are currently lacking. METHODS: Expression profiling of colon cancer were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of left- and right-sided colon cancers were compared by DESeq analysis. The prognostic values of DEGs were assessed by univariate and multivariate Cox regression. Prognostic index models of two side colon cancers were conducted with prognostic values genes, respectively. Interaction of DEGs was then analyzed by the protein-protein interaction (PPI). Different biology function of two sides of colon cancer was assessed by Gene Set Enrichment Analysis (GSEA). RESULTS: A total of 167 DEGs were identified between left- and right-sided colon cancers based on TCGA data. Using univariate COX regression analysis, five genes (PHACTR3, CKMT2, CYP2W1, ERFE, HOXC4) were related to overall survival in left-sided, and eight distinguishable genes (EREG, ERFE, HOXC6, SLC22A31, TFF1, GFI1, ZG16, RASL10B) in right-sided. Further, left-sided prognostic model was established with PHACTR3 and CKMT2 (HR=2.040; 95%CI=1.004-4.145; P=0.049). Distinguishable prognostic signature for right-sided colon cancer was established based on EREG, ERFE, GFI1, and RASL10B (HR=3.530; 95%CI: 1.934-6.444; P< 0.001) in multivariate analysis. PPI analysis of 167 DEGs showed that CCL5, GNG4, GNLY, GZMH, DRD2, and FASLG genes were at the core of interaction network. In GSEA function analysis, four pathways, including antigen processing and presentation, natural killer cell mediated cytotoxicity, intestinal immune network for Iga production, and type I diabetes mellitus, were significantly enriched in the DEGs of the right-sided colon cancer. CONCLUSIONS: This study constructs a panel of potential prognostic model of left- and right-sided colon cancers, respectively. We also provide molecular biological alterations between left- and right-sided colon cancers.


Assuntos
Neoplasias do Colo/patologia , Idoso , Área Sob a Curva , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Proteínas de Ligação a DNA/genética , Epirregulina/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hormônios Peptídicos/genética , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas , Curva ROC , Fatores de Transcrição/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA