scholarly journals miR-148a-3poverexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis

2016 ◽  
Vol 310 (6) ◽  
pp. C470-C478 ◽  
Author(s):  
Liu Qingjuan ◽  
Feng Xiaojuan ◽  
Zhang Wei ◽  
Wu Chao ◽  
Kang Pengpeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lupus Nephritis ◽  
Blood Serum ◽  
Mesangial Cells ◽  
High Mobility ◽  
Expression Level ◽  
Nuclear Antigen ◽  
Glomerular Cell

The objective of this study was to investigate the role of miR-148a-3p in lupus nephritis (LN) based on data from previous studies and a microRNA assay. We evaluated the miR-148a-3p expression level in LN renal tissues and blood serum to determine its clinicopathological significance and effect on glomerular cell proliferation. Then, we collected renal glomeruli from LN mice and determined the miR-148a-3p, proliferating cell nuclear antigen (PCNA), and PCNA/Thy1 expression. We performed functional analyses of miR-148a-3p in vitro and in vivo. We also investigated the target gene of miR-148a-3p in LN. The results showed that miR-148a-3p expression levels were significantly higher not only in glomeruli but also in the blood serum during LN and increased in the glomeruli of LN mice and that at the same time there was positive correlation between miR-148a-3p and PCNA expression of glomruli. Overexpression of miR-148a-3p accelerated cell proliferation and PCNA expression, while a miR-148a-3p inhibitor inhibited cell proliferation via the Akt/cyclin D1 pathway. Furthermore, miR-148a-3p overexpression reduced the phosphatase and tensin homology deleted on chromosome ten (PTEN) expression level, while miR-148a-3p silencing increased its expression in high-mobility group box 1 (HMGB1)-induced mouse mesangial cells (MMCs). Luciferase assays demonstrated that miR-148a-3p could directly bind to the PTEN 3′-UTR. PTEN overexpression inhibited MMC proliferation considerably, resembling the results observed during miR-148a-3p inhibition. Reducing miR-148a-3p expression upregulated PTEN in the glomeruli and improved renal function in LN mice. Thus miR-148a-3p may promote proliferation and contribute to LN progression by targeting PTEN.

scholarly journals MCOLN1 Promotes Proliferation and Predicts Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhan-Dong Hu ◽  
Jun Yan ◽  
Kai-Yue Cao ◽  
Zhi-Qi Yin ◽  
Wei-Wei Xin ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Expression Level ◽  
Nuclear Antigen ◽  
Ductal Adenocarcinoma ◽  
Proliferation Capacity ◽  
Late Endosomes ◽  
Tumor Tissues ◽  
High Level

Background. MCOLN1 (mucolipin subfamily, member 1) was first identified as an autophagic regulator, which was essential for efficient fusion of both autophagosomes and late endosomes with lysosomes. This study is aimed at investigating the role of MCOLN1 in the development of pancreatic ductal adenocarcinoma (PDAC). Methods. Immunohistochemistry (IHC) assay was conducted to evaluate the expression level of MCOLN1 in 82 human PDAC tumor tissues. Overall survival (OS) and recurrence-free survival (RFS) analysis was performed to assess the prognosis of patients. Colony formation and MTT assays [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] were performed to measure the proliferation capacity of tumor cells. The expression level of related genes was measured by RT-PCR (reverse transcription polymerase chain reaction) and western blot assays. The animal model was used to examine the effects of indicated protein on tumorigenesis in vivo. Results. The results of IHC showed that a high level of MCOLN1 expression was associated with the poor clinical characteristics of PDAC patients. OS and RFS were significantly worse in patients with high MCOLN1 expression. Silencing of MCOLN1 dramatically blocked the proliferation of PDAC cells. Mechanism studies confirmed that knockdown of MCOLN1 decreased the expression of Ki67 and PCNA (proliferating cell nuclear antigen), two markers of cell proliferation. In vivo, MCOILN1 depletion reduced the formation and growth of tumors in mice. Conclusion. The high level of MCOLN1 expression was associated with poor clinical outcomes of PDAC patients. MCOLN1 ablation could inhibit PDAC proliferation of both in vitro and in vivo, which provide a new insight and novel therapeutic target for the treatment of PDAC.

Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1235-L1241 ◽  
Author(s):  
John S. Kim ◽  
Valerie S. McKinnis ◽  
Kimberly Adams ◽  
Steven R. White
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Nuclear Antigen ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Injury Site ◽  
And Migration

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

scholarly journals Agmatine Inhibits Cell Proliferation and Improves Renal Function in Anti—Thy-1 Glomerulonephritis

2000 ◽  
Vol 11 (12) ◽  
pp. 2256-2264
Author(s):  
SHUNJI ISHIZUKA ◽  
ROBYN CUNARD ◽  
SIRIA POUCELL-HATTON ◽  
LUCINDA WEAD ◽  
MARK LORTIE ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Renal Function ◽  
Cellular Proliferation ◽  
Tissue Injury ◽  
Nuclear Antigen ◽  
Polyamine Biosynthesis ◽  
Reduce Cell Proliferation

Abstract. Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular 3H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model.

scholarly journals Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib

2021 ◽  
Vol 27 ◽  
Author(s):  
Fangling Hu ◽  
Liang Guo ◽  
Jieqing Yu ◽  
Daofeng Dai ◽  
Yuanping Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Nuclear Antigen ◽  
Tumor Tissues

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end.Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo.Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis.Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.

scholarly journals Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Reproduction ◽  
2013 ◽  
Vol 145 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Carla N Olivares ◽  
Mariela A Bilotas ◽  
Analía G Ricci ◽  
Rosa Inés Barañao ◽  
Gabriela F Meresman
Keyword(s):  
Cell Proliferation ◽  
Nuclear Antigen ◽  
Gynecological Disease ◽  
Cox 2 ◽  
Benign Gynecological Disease ◽  
Surgically Induced ◽  
Free Women ◽  
Proliferating Cell

Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and aromatase proteins have been shown to be overexpressed in eutopic endometrium from women suffering from this disease compared to disease-free women. Furthermore, inhibition of these molecules individually was demonstrated to have antiproliferative and proapoptotic effects both in vitro and in vivo in several models. In this study, the effect of combining celecoxib, a selective COX-2 inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and growth of endometriotic like lesions in a murine model of endometriosis was evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28 days of treatment with celecoxib, anastrozole, or their combination, animals were killed and lesions were counted, measured, excised, and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for assessment of cell proliferation and vascularization. TUNEL technique was performed for apoptosis evaluation. Celecoxib was the only treatment to significantly reduce the number of lesions established per mouse, their size and vascularized area. In addition, cell proliferation was significantly diminished and apoptosis was significantly enhanced by both individual treatments. When the therapies were combined, they reversed their effects. These results confirm that celecoxib and anastrozole separately decrease endometriotic growth, but when combined they might have antagonizing effects.

Suppression of C6 Gliomas via Application of Rat Hyperplasia Gene

2014 ◽  
Vol 29 (4) ◽  
pp. 411-422 ◽  
Author(s):  
Peng Gao ◽  
Zhanwei Wang ◽  
Bin Zhang ◽  
Yourui Zou ◽  
Hui Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Recombinant Adenovirus ◽  
Glioma Cells ◽  
In Vivo Studies ◽  
Nuclear Antigen ◽  
Sprague Dawley ◽  
Rat Glioma ◽  
Suppression Mechanism

Background Among all neurological tumors, tumor incidence of the neuroepithelial tissue is the highest, where 50% are gliomas. Treatment for gliomas has traditionally included surgery and adjuvant therapy. With advancements in medicine, gene therapy has entered the clinical setting, in which control of tumor growth, tumor volume and decrease of supply of blood to the tumor have been observed. Rat hyperplasia suppressor gene (rHSG) has been proven to inhibit the injury-mediated proliferation of vascular smooth muscle cells. Methods A recombinant adenovirus, Adv-rHSG-GFP, was constructed and characterized by in vitro and in vivo studies. The function of rHSG on cell proliferation was determined in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) exclusion assay and plate clone formation, while a C6/Sprague Dawley rat glioma model was established to observe the effect of rHSG in vivo. Results Overexpression of rHSG displayed a strong effect on suppressing C6 cells proliferation in vitro and growth of glioma in vivo, which suggests the use of rHSG as a possible treatment strategy for glioma. p21Cip1, p27Kip1 and proliferating cell nuclear antigen were found to be involved in the tumor suppression mechanism of rHSG. Conclusions rHSG can markedly inhibit of the growth of rat glioma cells. The suppression mechanism of rHSG may be related to cell cycle regulation, which shows that rHSG is a potential therapeutic target of glioma tumor. This preclinical study supports a further in-depth study on the effect of rHSG on cell proliferation, migration and change in the extracellular matrix component of glioma cells.

scholarly journals Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

2018 ◽  
Vol 46 (6) ◽  
pp. 2215-2231 ◽  
Author(s):  
Fengchang Qiao ◽  
Pihai Gong ◽  
Yunwei Song ◽  
Xiaohui Shen ◽  
Xianwei Su ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Expression Level ◽  
Qrt Pcr ◽  
Genome Wide ◽  
Patient Prognosis

Background/Aims: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood. Methods: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting. Results: The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genome-wide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis. Conclusion: Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

scholarly journals Fucoidan Inhibits the Progression of Hepatocellular Carcinoma via Causing lncRNA LINC00261 Overexpression

2021 ◽  
Vol 11 ◽  
Author(s):  
Danhui Ma ◽  
Jiayi Wei ◽  
Sinuo Chen ◽  
Heming Wang ◽  
Liuxin Ning ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
High Throughput Sequencing ◽  
Biological Activities ◽  
Expression Level ◽  
Sulfated Polysaccharides ◽  
High Morbidity ◽  
Liver Cancers

Hepatocellular carcinoma (HCC) as a main type of primary liver cancers has become one of the most deadly tumors because of its high morbidity and poor prognosis. Fucoidan is a family of natural, heparin-like sulfated polysaccharides extracted from brown algae. It is not only a widely used dietary supplement, but also participates in many biological activities, such as anti-oxidation, anti-inflammation and anti-tumor. However, the mechanism of fucoidan induced inhibition of HCC is elusive. In our study, we demonstrated that fucoidan contributes to inhibiting cell proliferation in vivo and in vitro, restraining cell motility and invasion and inducing cell cycle arrest and apoptosis. According to High-Throughput sequencing of long-non-coding RNA (lncRNA) in MHCC-97H cells treated with 0.5 mg/mL fucoidan, we found that 56 and 49 lncRNAs were correspondingly up- and down-regulated. LINC00261, which was related to the progression of tumor, was highly expressed in fucoidan treated MHCC-97H cells. Moreover, knocking down LINC00261 promoted cell proliferation by promoting the expression level of miR-522-3p, which further decreased the expression level of downstream SFRP2. Taken together, our results verified that fucoidan effectively inhibits the progression of HCC via causing lncRNA LINC00261 overexpression.

scholarly journals CircCDYL Acts as a Tumor Suppressor in Wilms’ Tumor by Targeting miR-145-5p

2021 ◽  
Vol 9 ◽  
Author(s):  
Rui Zhou ◽  
Wei Jia ◽  
Xiaofeng Gao ◽  
Fuming Deng ◽  
Kai Fu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Wilms Tumor ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Junction Protein

Circular RNAs (circRNA) have been reported to exert evident functions in many human carcinomas. However, the possible mechanisms concerning the circRNA in various tumors are still elusive. In this research, we analyzed the expression profile and biological functions of circular RNA CDYL (circCDYL, circBase ID: hsa_circ_0008285) in Wilms’ tumor. Here, miRNA and gene expression were examined by real-time PCR in Wilms’ tumor tissues and cell lines. The functions of circCDYL and its potential targets to influence cell proliferation, migration, and invasion in Wilms’ tumor cells were determined by biological functional experiments in vitro and in vivo. We predicted and analyzed potential miRNA targets through online bioinformatic tools. To validate the interactions between circCDYL and its targets, we performed RNA fluorescence in situ hybridization, biotin-coupled miRNA capture assay, and biotin-coupled probe pull-down assay. Tight junction protein l (TJP1) was proved to be the target gene of the predicted miRNA by dual-luciferase reporter assay. The expression level of TJP1 in Wilms’ tumor cells was identified via Western blot. We showed that circCDYL was downregulated in WT tissue compared with adjacent non-tumor tissue. Upregulation of circCDYL could reduce cell proliferation, migration, and invasion. Mechanically, circCDYL, functioning as a miRNA sponge, decreased the expression level of miR-145-5p and TJP1 3′UTR was validated as the target of miR-145-5p, facilitating the circCDYL/miR-145-5p/TJP1 axis. In conclusion, our study suggested circCDYL as a novel biomarker and therapeutic target for WT treatment.

scholarly journals NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Erhu Zhao ◽  
Liying Feng ◽  
Longchang Bai ◽  
Hongjuan Cui
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
High Mobility ◽  
Cancer Prognosis ◽  
Induce Cell Cycle Arrest ◽  
Kinase Substrate ◽  
Gastric Cancer Patients

Abstract Background Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001, is a member of the high mobility group (HMG) family. Although very little is known regarding the biological roles of NUCKS, emerging clinical evidence suggests that the NUCKS protein can be used as a biomarker and therapeutic target in various human ailments, including several types of cancer. Methods We first assessed the potential correlation between NUCKS expression and gastric cancer prognosis. Then functional experiments were conducted to evaluate the effects of NUCKS in cell proliferation, cell cycle, apoptosis and autophagy. Finally, the roles of NUCKS on gastric cancer were examined in vivo. Results We found that NUCKS was overexpressed in gastric cancer patients with poor prognosis. Through manipulating NUCKS expression, it was observed to be positively associated with cell proliferation in vitro and in vivo. NUCKS knockdown could induce cell cycle arrest and apoptosis. Then further investigation indicated that NUCKS knockdown could also significantly induce a marked increase in autophagy though the mTOR-Beclin1 pathway, which could be was rescued by NUCKS restoration. Moreover, silencing Beclin1 in NUCKS knockdown cells or adding rapamycin in NUCKS-overexpressed cells also confirmed these results. Conclusions Our findings revealed that NUCKS functions as an oncogene and an inhibitor of autophagy in gastric cancer. Thus, the downregulation or inhibition of NUCKS may be a potential therapeutic strategy for gastric cancer.

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