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1.
Biomed Res Int ; 2019: 7259691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428643

RESUMO

Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl2 treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.

2.
Mol Oncol ; 13(7): 1589-1604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31162799

RESUMO

Activation of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway induces glial differentiation of glioblastoma (GBM) cells, but the mechanism by which microRNA (miRNA) regulate this process remains poorly understood. In this study, by performing miRNA genomics and loss- and gain-of-function assays in dibutyryl-cAMP-treated GBM cells, we identified a critical negative regulator, hsa-miR-1275, that modulates a set of genes involved in cancer progression, stem cell maintenance, and cell maturation and differentiation. Additionally, we confirmed that miR-1275 directly and negatively regulates the protein expression of glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. Of note, tri-methyl-histone H3 (Lys27) (H3K27me3), downstream of the PKA/polycomb repressive complex 2 (PRC2) pathway, accounts for the downregulation of miR-1275. Furthermore, decreased miR-1275 expression and induction of GFAP expression were also observed in dibutyryl-cAMP-treated primary cultured GBM cells. In a patient-derived glioma stem cell tumor model, a cAMP elevator and an inhibitor of H3K27me3 methyltransferase inhibited tumor growth, induced differentiation, and reduced expression of miR-1275. In summary, our study shows that epigenetic inhibition of miR-1275 by the cAMP/PKA/PRC2/H3K27me3 pathway mediates glial induction of GBM cells, providing a new mechanism and novel targets for differentiation-inducing therapy.

4.
EMBO Mol Med ; 11(6)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31036704

RESUMO

Mutations to KRAS are recurrent in lung adenocarcinomas (LUAD) and are daunting to treat due to the difficulties in KRAS oncoprotein inhibition. A possible resolution to this problem may lie with co-mutations to other genes that also occur in KRAS-driven LUAD that may provide alternative therapeutic vulnerabilities. Approximately 3% of KRAS-mutant LUADs carry functional mutations in NF1 gene encoding neurofibromin-1, a negative regulator of focal adhesion kinase 1 (FAK1). We evaluated the impact of Nf1 loss on LUAD development using a CRISPR/Cas9 platform in a murine model of Kras-mutant LUAD We discovered that Nf1 deactivation is associated with Fak1 hyperactivation and phosphoserine aminotransferase 1 (Psat1) upregulation in mice. Nf1 loss also accelerates murine Kras-driven LUAD tumorigenesis. Analysis of the transcriptome and metabolome reveals that LUAD cells with mutation to Nf1 are addicted to glutamine metabolism. We also reveal that this metabolic vulnerability can be leveraged as a treatment option by pharmacologically inhibiting glutaminase and/or Psat1. Lastly, the findings advocate that tumor stratification by co-mutations to KRAS/NF1 highlights the LAUD patient population expected to be susceptible to inhibiting PSAT1.

5.
Cell Death Dis ; 10(5): 358, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043589

RESUMO

Given that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs.

6.
EBioMedicine ; 44: 138-149, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31105033

RESUMO

BACKGROUND: The influence of amyloid protein-binding protein 2 (APPBP2) on lung cancer is unknown. METHODS: The function and mechanisms of APPBP2 were investigated in the NSCLC cell lines A549 and H1299. The ectopic expression of APPBP2, PPM1D and SPOP in NSCLS were examined in samples collected from ten pairs of human lung adenocarcinoma cancer tissues and adjacent normal lung tissues. shRNA vector was used for APPBP2 knockdown. Quantitative PCR and western blot assays quantified the mRNA and protein level of APPBP2, PPM1D, and SPOP. Cell proliferation was measured with BrdU, MTT, colony formation assays, and xenograft tumour growth experiments. Cell migration and invasion were analysed with transwell and wound healing assays. Co-Immunoprecipitation assay detected protein-protein interactions. FINDINGS: APPBP2 was upregulated in NSCLC tissues. Silencing APPBP2 in A549 and H1299 cells resulted in the inhibition of cell proliferation, migration, and invasion, enhancement of apoptosis, and a significant decrease in the expression of PPM1D and SPOP. Overexpression of PPM1D and SPOP attenuated the APPBP2-knockdown inhibition of NSCLC cells. Co-IP assay showed that PPM1D interacted with APPBP2. INTERPRETATION: The expression level of APPBP2 positively correlates with NSCLC cell proliferation, migration, and invasiveness. APPBP2 contributes to NSCLC progression through regulating the PPM1D and SPOP signalling pathway. This novel molecular mechanism, underlying NSCLC oncogenesis, suggests APPBP2 is a potential target for diagnosis and therapeutic intervention in NSCLC. FUND: Key Program of Natural Science Research of Higher Education of Anhui Province (No. KJ2017A241), the National Natural Science Foundation of China (No. 81772493).

7.
Biochem Biophys Res Commun ; 513(4): 904-911, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31005252

RESUMO

BACKGROUND: Non-small cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we report on the role of circP4HB in NSCLC. METHODS: First, we evaluated circP4HB levels in patient-derived NSCLC tissue versus paired healthy samples. Next, we conducted experiments in vitro in NSCLC cell-lines and in vivo in a murine xenograft NSCLC model to assess the impact of circP4HB on epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. The downstream impact of circP4HB on the microRNA miR-133a-5p, and its target the EMT marker vimentin, were also evaluated. RESULTS: NSCLC tumor specimens exhibited higher circP4HB levels in comparison to paired healthy lung samples and was associated with metastatic disease and poorer survival. circP4HB promoted EMT and vimentin expression in vitro and xenograft metastasis in vivo through sequestration of miR-133a-5p. CONCLUSION: circP4HB enhances EMT and metastatic disease through miR-133a-5p sequestration, leading to upregulation of vimentin. Therefore, these findings advocate targeting the circP4HB/miR-133a-5p/vimentin axis as a potential therapeutic option for NSCLC patients.

8.
Artif Cells Nanomed Biotechnol ; 47(1): 548-554, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30849921

RESUMO

Thyroid cancer is now the most common endocrine malignancy and the effect of miR-429 in the development of thyroid cancer still need to be further investigated. The expression level of miR-429 was quantified by qPCR in both clinical samples and cultured cell lines. MTT, flow cytometry, migration analyses and Matrigel invasion assays were conducted to test the proliferation, apoptosis, migration and invasion of MiR-429 transfection in thyroid cancer cell lines. Luciferase activity assay and western blot were conducted to detect the direct effect of miR-429 on Zinc finger E-box-binding homeobox 1 (ZEB1) expression. In this study, it was found that miR-429 was frequently decreased in thyroid cancer tissues and cell lines. Transfection of miR-429 in thyroid cancer cell lines substantially suppressed cell proliferation, migration and invasion. Besides, miR-429 up-regulation would induce apoptosis in different cell lines. ZEB1 was identified as a direct target of miR-429 and miR-429 transfection could inhibit ZEB1 by direct binding to its 3'-untranslated region (3'-UTR). In conclusion, these data indicated that miR-429 could act as a tumour suppressor miRNA and contribute to the development and progression and metastasis of thyroid cancer.


Assuntos
Apoptose/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação para Baixo , Humanos , Invasividade Neoplásica
9.
Clin Exp Pharmacol Physiol ; 46(6): 556-566, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30854677

RESUMO

Noise-induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over-activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20-20k Hz, 90-110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.

10.
Cancer Lett ; 447: 56-65, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30685413

RESUMO

L1 cell adhesion molecule (L1CAM) promotes invasiveness and metastasis in non-small cell lung cancer (NSCLC) cells and is upregulated by the p53-regulated transcription factor Slug. p21-activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro-malignant Slug stabilization. We hypothesized that microRNA-based negative regulation of PAK4 would reduce L1CAM-induced NSCLC aggressiveness via destabilizing Slug. We found that elevated L1CAM expression was tightly correlated with p53 loss-of-function and reduced NSCLC patient survival. L1CAM suppression reduced NSCLC cell migration and invasiveness in vitro as well as tumor formation and distal metastasis in vivo. Mechanistically, p53 restricts L1CAM expression through the ß-catenin/Slug pathway, with levels of ß-catenin and Slug positively correlating with L1CAM expression in NSCLC tumors. The microRNA miR-193a-3p directly targets PAK4 and suppresses downstream p-Slug and L1CAM expression. Silencing PAK4, Slug, and L1CAM mirrored miR-193a-3p's effects upon the migration and invasiveness of NSCLC cells in vitro. Decreased miR-193a-3p levels correlated with elevated PAK4, p-Slug, and L1CAM levels in NSCLC tumors. Our findings support a model of miR-193a-3p as a suppressor of metastatic disease progression in NSCLC via modulation of the p53/Slug/L1CAM pathway.

11.
Appl Opt ; 57(33): 9877-9886, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30462023

RESUMO

In this paper, an aberration correction method for an extended target is proposed to solve the problem of the lenslet-based plenoptic camera not imaging clearly under the influence of aberrations. We propose a light field manipulation method to improve performance of the light field imaging system. The principle of this method is that the sub-aperture images extracted from the raw light field image are offset when the light field imaging system is affected by aberrations, and the symmetrical arrangement of the sub-aperture image array is destroyed. By repairing the symmetrical arrangement of the sub-aperture image array, the influence of phase aberrations on the imaging system can be eliminated, and the resolution of the plenoptic camera can be improved. We use an image correlation algorithm to process the sub-aperture images of the plenoptic camera, calculate and compensate each sub-aperture image's displacement caused by aberrations, and restore the symmetrical arrangement of the sub-aperture image array; then, a corrected high-resolution refocused image can be generated. In particular, this method uses only the raw light field information obtained by the plenoptic camera in a single exposure, without adding other hardware devices. Furthermore, it takes the extended target itself as the reference image, so the ideal position need not be calibrated in advance. Also, the parallax information of the sub-aperture images is retained, and the method is simple and easy to use. Numerical simulation and experimental results show that the technology proposed in this paper can work well for high-resolution imaging of a plenoptic camera with phase aberrations. This method can be potentially applied to analyze lens aberration, media-induced image distortion such as water turbulence in underwater imaging, and atmospheric turbulence in remote imaging. It may have important application prospects in the fields of astronomical object detection, remote sensing, etc.

12.
Cell Physiol Biochem ; 51(2): 991-1000, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30466107

RESUMO

BACKGROUND/AIMS: To investigate the role of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in the clinical prognosis and cell biology of renal cell carcinoma (RCC). METHODS: A total of 137 RCC tissues were evaluated by immunohistochemistry. The relationship between MTHFD2 overexpression and clinical parameters and vimentin expression was assessed. Kaplan-Meier curves and the log-rank test were applied for survival analysis according to MTHFD2 and vimentin expression in RCC tissues. The expression of MTHFD2 mRNA and protein was examined by quantitative reverse transcription PCR and western blotting, respectively. To determine further the biological activity of MTHFD2 in RCC, 786-O cells were transfected with short hairpin RNA specifically targeting MTHFD2 (shMTHFD2) with or without tumor necrosis factor (TNF)-α stimulation. Cell proliferation, cell migration and invasion and drug sensitivity were subsequently assessed using Cell Counting Kit-8, wound healing, and Transwell assays. RESULTS: Immunohistochemical analysis demonstrated that both MTHFD2 and vimentin overexpression was positively associated with clinical staging, pathological grade, and poor overall survival (all P < 0.05). MTHFD2 expression was closely correlated with vimentin overexpression in RCC (r = 0.402, P < 0.001). After knocking down MTHFD2 expression in 786-O cells, decreased cell proliferation, migration, and invasion were observed and accompanied by the reduced expression of vimentin. The effects of MTHFD2 down-regulation could be partially restrained by TNF-α treatment. Vimentin expression and cell migration and invasion, but not cell proliferation, were reversed by TNF-α stimulation. Furthermore, treatment of 786-O cells with shMTHFD2 increased their sensitivity to chemotherapy drugs. CONCLUSION: The current results demonstrated that MTHFD2 was overexpressed in RCC and associated with poor clinical characteristics, vimentin expression, and cellular features connected to malignant disease, thus, implicating MTHFD2 as a potential target for RCC therapy.

13.
Oncol Lett ; 16(2): 2009-2015, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30034553

RESUMO

Papillary thyroid carcinoma (PTC) is the most common form of non-medullary thyroid cancer, accounting for ~80% of all cases of thyroid cancer. The aim of the present study was to explore the role of BRAF-activated long noncoding RNA (BANCR) in the development of PTC. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BANCR, thyroid-stimulating hormone receptor (TSHR) and cyclin D1 between PTC and benign control thyroid nodule tissue samples from 60 patients were determined. Using RT-qPCR and western blot analysis, the expression levels of TSHR and cyclin D1 mRNA and protein were determined in cells transfected with BANCR-small interfering (si)RNA. An MTT assay and flow cytometry were used to analyze the effect of BANCR knockdown on the proliferation and cell cycle distribution of IHH-4 PTC cells. The expression of BANCR, TSHR and cyclin D1 was increased in the PTC group compared with the control group based on the RT-qPCR data. The transfection of IHH-4 cells with BANCR-siRNA induced the inhibition of TSHR and cyclin D1 expression compared with a transfection control. In addition, the proliferation of the IHH-4 cells transfected with BANCR-siRNA was suppressed, relative to the transfection control, and cells arrested in the G0/G1 phase, potentially due to the inhibition of the expression of cyclin D1. The data suggested that the expression of BANCR may promote the development of malignant thyroid nodules via the modulation of TSHR expression and its downstream effector, cyclin D1.

14.
Nat Commun ; 9(1): 1524, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29670091

RESUMO

Oncolytic virus is an attractive anticancer agent that selectively lyses cancer through targeting cancer cells rather than normal cells. Although M1 virus is effective against several cancer types, certain cancer cells present low sensitivity to it. Here we identified that most of the components in the cholesterol biosynthesis pathway are downregulated after M1 virus infection. Further functional studies illustrate that mevalonate/protein farnesylation/ras homolog family member Q (RHOQ) axis inhibits M1 virus replication. Further transcriptome analysis shows that RHOQ knockdown obviously suppresses Rab GTPase and ATP-mediated membrane transporter system, which may mediate the antiviral effect of RHOQ. Based on this, inhibition of the above pathway significantly enhances the anticancer potency of M1 virus in vitro, in vivo, and ex vivo. Our research provides an intriguing strategy for the rational combination of M1 virus with farnesyl transferase inhibitors to enhance therapeutic efficacy.

15.
Oncotarget ; 8(43): 74129-74138, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088773

RESUMO

To determine the extent to which thyroid stimulating hormone receptor (TSHR) mRNA in peripheral blood (PB) has diagnostic value for papillary thyroid carcinoma (PTC). We obtained pre- and postoperative PB samples from 104 thyroid disease patients and collected 11 healthy volunteers' PB samples twice apiece at different times. We used reverse transcription polymerase chain reaction (RT-PCR) to quantify TSHR mRNA expression levels in the samples. T-test and chi-square test were used to compare quantitative data and rates. The mean preoperative PB TSHR mRNA expression level of the PTC patients was significantly higher than that of the healthy volunteers. However, on the postoperative day 1, PB TSHR mRNA level of PTC patients significantly decreased but not for healthy controls. Preoperative PB TSHR mRNA expression levels were significantly associated with patient age, capsular invasion status, lymph node metastasis status, and BRAFV600E mutation status (P < 0.05) but not gender, tumor size, number of cancer foci, or Hashimoto thyroiditis status. Preoperative assessment of the PB TSHR mRNA expression level combined with ultrasonography of the thyroid had better accuracy in the diagnosis of PTC than either method alone did. Moreover, TSHR mRNA expression significantly affected recurrence of PTC patients. Our findings suggest that PB TSHR mRNA expression level is a promising novel biomarker for the early detection, diagnosis, and treatment of PTC. It may serve as a noninvasive means of PTC detection and a prognostic biomarker of residual tumor and help guide further treatment.

16.
Cell Prolif ; 50(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28963738

RESUMO

OBJECTIVES: Hypermethylation-induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA-142 (miR-142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR-142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC). METHODS: Hepatocellular carcinoma tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-142 and TGF-ß in two HCC cell lines were determined. The miRNA-mRNA network of miR-142 was analysed in HCC cell lines. RESULTS: We found that the miR-142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR-142 was identified to directly target and inhibit transforming growth factor ß (TGF-ß), leading to decreased cell vitality, proliferation, EMT and the ability of pro-angiogenesis in TGF-ß-dependent manner. Interestingly, the status of methylation of miR-142 was analysed and the results found the hypermethylated miR-142 in tumour patients and cell lines. The treatment of methylation inhibitor 5-Aza could restore the expression of miR-142 to suppress the TGF-ß expression, which impaired TGF-ß-induced tumour growth. CONCLUSION: These findings implicated that miR-142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF-ß-induced development of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética/genética , Humanos , Metástase Neoplásica , Neovascularização Patológica/genética
17.
Tumour Biol ; 39(6): 1010428317709128, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28639884

RESUMO

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus-related hepatocellular carcinoma metastases.


Assuntos
Proteínas ADAM/biossíntese , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/biossíntese , MicroRNAs/genética , Proteínas ADAM/genética , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Cateterismo Periférico , Movimento Celular/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células Hep G2 , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Proteínas de Membrana/genética , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Metástase Neoplásica , Ativação Transcricional/genética
18.
Am J Cancer Res ; 7(3): 554-564, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28401011

RESUMO

Novel metastasis-promoting gene 1 (NVM-1) has a significantly elevated protein level in a variety of tumor tissues and is involved in metastasis. However, its functions in hepatocellular carcinoma (HCC) are not clear. The current study aimed to investigate the functions of NVM-1 in cell proliferation, apoptosis, and epithelial-mesenchymal transition in HCC. NVM-1 protein expression in HCC was assessed by immunohistochemical staining. In vitro, cell proliferation, apoptosis, and aggressiveness were determined by CCK-8, fluorescence-assisted cell sorting, TdT-UTP nick-end labeling, and transwell assays, respectively. For in vivo studies, NVM-1 knockdown HCC cells were transplanted into BALB/c nude mice. NVM-1 was frequently upregulated in HCC tissues and positive NVM-1 expression was linked with poor prognosis. NVM-1 depletion significantly inhibited cell proliferation, migration, and invasion abilities in vitro and in vivo. Apoptosis was induced after NVM-1 knockdown. In conclusion, positive NVM-1 expression confers poor prognosis to HCC patients and the NVM-1 protein level correlates with HCC cell proliferation, apoptosis, and EMT.

19.
World J Gastroenterol ; 23(10): 1920-1924, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28348499

RESUMO

Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the alimentary tract. These tumors may have different clinical and biological behaviors. Malignant forms usually spread via a hematogenous route, and lymph node metastases rarely occur. Herein, we report a patient with a jejunal GIST who developed supraclavicular lymph node metastasis. We conclude that lymphatic diffusion via the mediastinal lymphatic station to the supraclavicular lymph nodes can be a potential metastatic route for GISTs.


Assuntos
Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/patologia , Melena/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Biópsia por Agulha , Quimioterapia Adjuvante , Transfusão de Eritrócitos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/uso terapêutico , Jejuno/patologia , Jejuno/cirurgia , Linfonodos/patologia , Metástase Linfática , Masculino , Melena/terapia , Pessoa de Meia-Idade , Esvaziamento Cervical , Gradação de Tumores , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Ultrassonografia
20.
Oncotarget ; 8(6): 10510-10522, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28060737

RESUMO

Ubiquitin-like with plant homeodomain and ring finger domains, 1 (UHRF1) is overexpressed in a variety of tumor tissues and is negatively correlated with prognosis of patients with cancers, yet so far, a comprehensive study of UHRF1 in hepatocellular carcinoma (HCC) has not been conducted. The present study was designed to explore the expression of UHRF1, associated clinical implications, and its possible functions in HCC. Reverse transcription-polymerase chain reaction and immunohistochemical staining were used to detect UHRF1 expression in HCC specimens including cancerous and noncancerous tissues. Associations of UHRF1 expression with demographic and clinicopathologic features in HCC were analyzed, and the effects of RNA interference of UHRF1 on cell proliferation, cell cycle, apoptosis, and migration were investigated in vitro and in vivo. UHRF1 mRNA and protein expression were both upregulated and negatively correlated with prognosis in HCC patients. Furthermore, inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression were observed in vitro and in vivo after UHRF1 knockdown, moreover, G2/M arrest was detected in HCC cells. In conclusion, elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas/metabolismo , Idoso , Animais , Apoptose , Biomarcadores Tumorais/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Transição Epitelial-Mesenquimal , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Regulação para Cima
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