scholarly journals β-catenin knockdown inhibits pituitary adenoma cell proliferation and invasion via interfering with AKT and gelatinases expression

2015 ◽  
Vol 46 (4) ◽  
pp. 1643-1650 ◽  
Author(s):  
CHENGCHENG ZHAO ◽  
MENG ZHANG ◽  
WENLAN LIU ◽  
CHUANFANG WANG ◽  
QIUSHENG ZHANG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pituitary Adenoma ◽  
Adenoma Cell ◽  
Proliferation And Invasion

scholarly journals Neuromedin B Receptor Antagonist Suppresses Pomc Expression in AtT-20 Cells and Human Corticotroph Adenoma Cells

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A546-A547
Author(s):  
Tomonori Sekizaki ◽  
Hiraku Kameda ◽  
Akinobu Nakamura ◽  
Hiroshi Nomoto ◽  
Kyu Yong Cho ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pituitary Adenoma ◽  
Mrna Expression ◽  
Real Time ◽  
Hormone Secretion ◽  
Corticotroph Adenoma ◽  
Adenoma Cell ◽  
Pomc Mrna ◽  
Post Hoc ◽  
Real Time Qpcr

Abstract Objective: We previously reported that Neuromedin B (NMB) is expressed in murine pituitary corticotrophs under adrenal insufficiency (1). Because NMB is also expressed in several cancer cells and stimulates ACTH secretion, we hypothesized that NMB is related to corticotroph adenoma cell proliferation and hormone secretion. To examine this hypothesis, we investigated the expression of NMB and its receptor NMBR in human corticotroph adenoma and the effects of a NMBR antagonist on AtT-20 cells, a mouse corticotroph adenoma cell line, and patient-derived corticotroph adenoma cells. Methods: 1. NMB and NMBR expression in human pituitary adenoma: We performed real-time qPCR and immunostaining on human pathological specimens of corticotrophs, somatotrophs, and non-functioning pituitary adenoma to investigate NMB and NMBR expression. 2. Experiments in AtT-20 cells: We extracted mRNAs and proteins from AtT-20 cells after incubation with 100nM NMBR antagonist PD168368, and performed real-time qPCR and western blotting analyses to investigate Pomc expression. 3. Experiments in patient-derived corticotroph adenoma cells: We isolated surgically resected human corticotroph adenoma cells from patients who underwent trans-sphenoidal surgery and investigated POMC mRNA expression by real-time qPCR after incubation with PD168368. Statistical analysis: One-way ANOVA was employed to compare values among multiple groups. If the ANOVA revealed significant differences, the Tukey-Kramer post-hoc test was employed to compare values between two specific groups. Dunnett’s post-hoc test was employed to compare values with the control group. Statistical significance was defined as p < 0.05. Results: 1. NMB and NMBR expression levels were significantly higher in human corticotroph adenoma (13 and 33 times higher than non-functioning adenoma, respectively) than in somatotroph adenoma (2 and 3 times higher than non-functioning adenoma, respectively) and non-functioning adenoma in the qPCR analyses. Immunostaining confirmed higher expression of NMB and NMBR in corticotroph adenoma than in somatotroph and non-functioning adenoma. 2. Treatment with 100 nM PD168368 significantly suppressed Pomc mRNA and protein expression in AtT-20 cells by 22%±3% and 25%±10%, respectively. 3. Treatment with 1 µM PD168368 significantly suppressed POMC mRNA expression in human corticotroph adenoma cells by 18%±1%. Conclusions: NMB and NMBR were both expressed in human corticotroph adenoma, suggesting that NMB may stimulate adenoma cell proliferation and hormone secretion in autocrine or paracrine manners. Because the NMBR antagonist suppressed Pomc expression in both AtT-20 cells and human corticotroph adenoma cells, it may represent a potential treatment for Cushing disease. Reference: (1) Kameda H et al., Endocrinology 2014;155(7):2492-9.

scholarly journals Down-regulation LncRNA-SNHG15 contributes to proliferation and invasion of bladder cancer cells

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aldhabi Mokhtar ◽  
Chuize Kong ◽  
Zhe Zhang ◽  
Yan Du
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Tumor Stage ◽  
Rt Pcr ◽  
Down Regulation ◽  
Bladder Cancer Cells ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Abstract Objectives The aim of this study was to investigate the effect of lncRNA-SNHG15 in bladder carcinoma using cell lines experiments and the relationship between clinical characteristics and lncRNA-SNHG15 expression was analyzed. Methods Bladder cancer tissues and near-cancer tissues were collected. The real-time PCR (RT-PCR) was used to detect the expression of lncRNA-SNHG15 in tissues and cell lines. The expression of lncRNA-SNHG15 was downregulated by interference (siRNA), as detected by RT-PCR, that was used to determine the efficiency of the interference. CCK-8 and Transwell assays were used to evaluate the effect of lncRNA-SNHG15 on the proliferation and invasion capability of bladder cancer cells. The t-test was used for Statistical analyses, which were carried out using the Statistical Graph pad 8.0.1.224 software. Result The expression of lncRNA-SNHG15 was up regulated in 5637, UMUC3 and T24 cell lines compared with corresponding normal controls (P < 0.05). Up regulation was positively related to tumor stage (P = 0.015). And tumor size (P = 0.0465). The down-regulation of lncRNA-SNHG15 with siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion. Conclusion This study showed that lncRNA-SNHG15 is overexpressed in bladder cancer tissues and (5637, UMUC3 T24) cell lines. Up regulation was positively related to tumor stage (P = 0.015), and tumor size (P = 0.0465). Down-regulation of lncRNA-SNHG15 by siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion, indicating a potential molecular target for future tumor targeted therapy.

scholarly journals LncRNA PCAT1 Interacts with DKC1 to Regulate Proliferation, Invasion and Apoptosis in NSCLC Cells via the VEGF/AKT/Bcl2/Caspase9 Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972098607
Author(s):  
Shi-Yuan Liu ◽  
Zhi-Yu Zhao ◽  
Zhe Qiao ◽  
Shao-Min Li ◽  
Wei-Ning Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Rna Binding ◽  
A549 Cells ◽  
Nonsmall Cell Lung Cancer ◽  
Nsclc Cell ◽  
Loss Of Function ◽  
Proliferation And Invasion

Long noncoding RNAs (lncRNAs) are increasingly recognized as indispensable components of the regulatory network in the progression of various cancers, including nonsmall cell lung cancer (NSCLC). The lncRNA prostate cancer associated transcript 1 (PCAT1) has been involved in tumorigenesis of multiple malignant solid tumors, but it is largely unknown that what is the role of lncRNA-PCAT1 and how it functions in the progression of lung cancer. Herein, we observed that lncRNA PCAT1 expression was upregulated in both human NSCLC tissues and cell lines, which was determined by qualitative polymerase chain reaction analysis. Then, gain-and loss-of-function manipulations were performed in A549 cells by transfection with a specific short interfering RNA against PCAT1 or a pcDNA-PCAT1 expression vector. The results showed that PCAT1 not only promoted NSCLC cell proliferation and invasion but also inhibited cell apoptosis. Bioinformatics and expression correlation analyses revealed that there was a potential interaction between PCAT1 and the dyskerin pseudouridine synthase 1 (DKC1) protein, an RNA-binding protein. Then, RNA pull-down assays with biotinylated probes and transcripts both confirmed that PCAT1 directly bounds with DKC1 that could also promote NSCLC cell proliferation and invasion and inhibit cell apoptosis. Moreover, the effects of PCAT1 and DKC1 on NSCLC functions are synergistic. Furthermore, PCAT1 and DKC1 activated the vascular endothelial growth factor (VEGF)/protein kinase B (AKT)/Bcl-2/caspase9 pathway in NSCLC cells, and inhibition of epidermal growth factor receptor, AKT, or Bcl-2 could eliminate the effect of PCAT1/DKC1 co-overexpression on NSCLC cell behaviors. In conclusion, lncRNA PCAT1 interacts with DKC1 to regulate proliferation, invasion, and apoptosis in NSCLC cells via the VEGF/AKT/Bcl-2/caspase9 pathway.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

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