scholarly journals High expression of PSMC2 promotes gallbladder cancer through regulation of GNG4 and predicts poor prognosis

Oncogenesis ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Dawei Zhu ◽  
Xing Gu ◽  
Zhengyu Lin ◽  
Dandan Yu ◽  
Jing Wang
Keyword(s):  
Gallbladder Cancer ◽  
Malignant Tumor ◽  
Xenograft Model ◽  
Tumor Grade ◽  
Significant Inhibition ◽  
Mechanistic Study ◽  
Downstream Target ◽  
Advanced Tumor

AbstractGallbladder cancer (GBC) is a common malignant tumor of the biliary tract, which accounts for 80–95% of biliary tumors worldwide, and is the leading cause of biliary malignant tumor-related death. This study identified PSMC2 as a potential regulator in the development of GBC. We showed that PSMC2 expression in GBC tissues is significantly higher than that in normal tissues, while high PSMC2 expression was correlated with more advanced tumor grade and poorer prognosis. The knockdown of PSMC2 in GBC cells induced significant inhibition of cell proliferation, colony formation and cell motility, while the promotion of cell apoptosis. The construction and observation of the mice xenograft model also confirmed the inhibitory effects of PSMC2 knockdown on GBC development. Moreover, our mechanistic study recognized GNG4 as a potential downstream target of PSMC2, knockdown of which could aggravate the tumor suppression induced by PSMC2 knockdown in vitro and in vivo. In conclusion, for the first time, PSMC2 was revealed as a tumor promotor in the development of GBC, which could regulate cell phenotypes of GBC cells through the interaction with GNG4, and maybe a promising therapeutic target in GBC treatment.

scholarly journals Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Zhinan Ren ◽  
Jun Li ◽  
Shanwen Zhao ◽  
Qi Qiao ◽  
Runguang Li
Keyword(s):  
Cell Proliferation ◽  
Tumor Grade ◽  
Mechanistic Study ◽  
Osteosarcoma Cell ◽  
Downstream Target ◽  
Normal Tissues ◽  
Advanced Tumor ◽  
Regulatory Effects

AbstractOsteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.

scholarly journals Salinomycin Exerts Anticancer Effects on PC-3 Cells and PC-3-Derived Cancer Stem Cells In Vitro and In Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yunsheng Zhang ◽  
Luogen Liu ◽  
Fang Li ◽  
Tao Wu ◽  
Hongtao Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Xenograft Model ◽  
Mechanistic Study ◽  
Prostate Cell ◽  
Downstream Target ◽  
Prostate Cancer Stem Cells

Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs). However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells. An in vivo experiment confirmed that salinomycin suppressed tumorigenesis in a NOD/SCID mice xenograft model generated from implanted PC-3 cells by inhibiting the Wnt/β-catenin pathway, since the total β-catenin protein level was reduced and the downstream target c-Myc level was significantly downregulated. We also showed that salinomycin, but not paclitaxel, triggered more apoptosis in aldehyde dehydrogenase- (ALDH-) positive PC-3 cells, which were considered as the prostate cancer stem cells, suggesting that salinomycin may be a promising chemotherapeutic to target CSCs. In conclusion, this study suggests that salinomycin reduces resistance and relapse of prostate tumor by killing cancer cells as well as CSCs.

scholarly journals DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chin-Hui Lai ◽  
Kexin Xu ◽  
Jianhua Zhou ◽  
Mingrui Wang ◽  
Weiyu Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Tumor Grade ◽  
In Vivo Studies ◽  
Mechanistic Study ◽  
Tumor Promotor ◽  
Bladder Cancer Cells

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.

AKT Activity Regulates Sensitivity of Multiple Myeloma Cells to mTor Inhibitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 646-646
Author(s):  
Patrick Frost ◽  
Bao Hoang ◽  
Joseph Gera ◽  
Anushree Sharma ◽  
Yijiang Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Significant Inhibition ◽  
Differential Sensitivity ◽  
Angiogenic Factor ◽  
Inhibition Of Proliferation ◽  
In Vivo Growth

Abstract Inhibitors of the mammalian target of rapamycin (mTOR), such as rapamycin and CCI-779, have potential as anti-tumor agents against multiple myeloma (MM). In a murine xenograft model, CCI-779 demonstrated efficacy against in vivo growth of OPM-2 and 8226 MM cells. In this model, OPM-2 tumors (ED50=2 mg/kg) were considerably more sensitive than 8226 (ED50=20 mg/kg) tumors. CCI-779-induced anti-tumor responses were associated with significant inhibition of proliferation and angiogenesis and concomitant upregulation of apoptosis. OPM-2 cells were also significantly more sensitive to these CCI-779-mediated effects. Other tumor models have demonstrated that heightened AKT activity induces hypersensitivity to mTOR inhibitors. As OPM-2 cells express high levels of activated AKT (due to PTEN mutations) and 8226 cells contain predominantly quiescent AKT, this regulatory role for AKT may be present in MM cells as well. To further test this, we stably expressed an activated AKT allele in U266 (U266myr-AKT) MM cells. The in vivo growth of U266myr-AKT cells was considerably more sensitive than control U266 cells to the anti-tumor effects of CCI-779. The differential sensitivity induced by AKT activation was mirrored in an enhanced sensitivity to CCI-779-mediated apoptosis and inhibition of angiogenesis. Since previous studies demonstrated the ability of AKT/mTOR to regulate the expression of vascular endothelial growth factor (VEGF), we hypothesized that MM cells with heightened AKT activity may be more sensitive to the CCI-779-mediated inhibition of this critical angiogenic factor. In vitro, mTOR inhibitor, rapamycin, was markedly more effective at inhibiting VEGF secretion from U266myr-AKT than control cells. Our results demonstrate that AKT regulates the sensitivity of MM cells to the anti-tumor effects of mTOR inhibitors and that this may be mediated through the inhibition of AKT-dependent survival and growth factors.

scholarly journals PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shi-Zhe Zhang ◽  
Xiao-Dong Zhu ◽  
Long-Hai Feng ◽  
Xiao-Long Li ◽  
Xue-Feng Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Apoptosis ◽  
Xenograft Model ◽  
Disease Free Survival ◽  
High Expression ◽  
Cell Counting ◽  
Mechanistic Study ◽  
Cell Cycle Distribution

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC). Methods Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis. Results High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway. Conclusions PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.

scholarly journals Pseudogene OCT4-pg5 Upregulates OCT4B Expression To Promote Bladder Cancer Progression By Competing With miR-145

2021 ◽  
Author(s):  
Wuer Zhou ◽  
Yue Yang ◽  
Wei Wang ◽  
Chenglin Yang ◽  
Zhi Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
In Vivo Experiments ◽  
Bladder Cell ◽  
Advanced Tumor

Abstract Background Octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) contributes to tumor progression in many cancer types, but contributions to bladder cancer (BC) have not been investigated. Methods Real-time quantity PCR (RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145 on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle stage distribution of T24 cells. Results OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145 suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.

scholarly journals Long Noncoding RNA PVT1 promoted Gallbladder Cancer proliferation Byepigenetically Suppressing mIR-18b-5p via DNA Methylation

2020 ◽  
Author(s):  
Longyang Jin ◽  
Qiang Cai ◽  
Shouhua Wang ◽  
Shuqing Wang ◽  
Jiandong Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gallbladder Cancer ◽  
Noncoding Rna ◽  
Methylation Status ◽  
Biliary Tree ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Downstream Target

Abstract Background Gallbladder cancer (GBC) accounts for 85–90% malignancies of the biliary tree worldwide. Considerable evidence has demonstrated that dysregulation of lncRNAs are involved in the progression of cancer. LncRNA PVT1 has been reported to play important roles in various cancers, but the role of PVT1 in gallbladder cancer remains unknown. Methods QRT-PCR was used to assess the expression of genes in different tissues or cells. Knockdown or overexpression of PVT1 combined with in vitro and in vivo assays were conducted to determine the effect of PVT1 on the GBC cells proliferation. We also conducted microarray analysis to screen out the miRNA that was regulated by PVT1. BSP was used to detect the methylation status of miR-18b-5p DNA promoter. RIP, ChIP, Co-IP and luciferase reporter assays were performed to validate the association between genes or proteins. Results We found that PVT1 was upregulated in GBC tissues and cells, and its upregulation was related with poor prognosis in GBC patients. PVT1 promoted GBC cells proliferation and increased tumorigenicity in nude mice. Molecular experiments demonstrated that PVT1 recruited DNMT1 via EZH2 to the miR-18b-5p DNA promoter and suppressed the transcription of miR-18b-5p through DNA methylation. Moreover, HIF1A was proved to be the downstream target gene of miR-18b-5p and PVT1 regulated GBC cell proliferation via HIF1A. Conclusions Our studies clarified the PVT1/ miR-18b-5p/ HIF1A regulation axis and indicated that PVT1 could be a potential therapeutic target for GBC.

scholarly journals Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis

2020 ◽  
Author(s):  
Zhongzheng Sun ◽  
Hao Xue ◽  
Yan Wei ◽  
Shaobo Wang ◽  
Jianye Xu ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Xenograft Model ◽  
Glioma Cells ◽  
Tumor Grade ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Orthotopic Xenograft Model ◽  
High Expression Group

Abstract Background: Ribosomal Protein S27-Like is an evolutionarily conserved ribosomal protein and the role of RPS27L influencing the malignance of several cancers has been reported. However, its effects on glioma were still unknown. This investigation aims to characterize the clinical significance and the biological functions of RPS27L in gliomas.Methods: TCGA databases were explored to analyze the correlation between RPS27L expression and the clinical characteristics of glioma patients. Immunohistochemical staining was performed on glioma cases and normal brain tissues. The function of RPS27L in glioma was further explored using U87MG and A172 cell lines and a orthotopic xenograft model of nude mice.Results: Data obtained from TCGA database showed higher expression of RPS27L in glioma than normal, and the overall survival was lower in the high expression group. Immunohistochemistry showed the expression levels of RPS27L were increased with the tumor grade rising in gliomas. Functional assays showed knockdown of RPS27L inhibited proliferation, cell cycle transition, migration and invasion, while promoted apoptosis. Data of western blot indicated that knockdown of RPS27L increased the level of p21，Bax and Cleaved Caspase-3 while decreased the level of CDK4, cyclinD1, cyclinE1, Bcl-2 and MMP2, MMP9 in glioma cells. In vivo, the growth of orthotopic glioma xenografts was suppressed by expression of RPS27L shRNA, and the tumors with RPS27L shRNA showed less aggressiveness and reduced expression of Ki67, Bcl-2 and MMP2. Conclusions: RPS27L is overexpressed in glioma cells. Knockdown of RPS27L could inhibit the proliferation, migration and invasion while promote apoptosis of glioma cells in vitro and in vivo. RPS27L might be a potential prognostic biomarker and possible target for future therapy in glioma.

scholarly journals Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis

2020 ◽  
Author(s):  
Zhongzheng Sun ◽  
Hao Xue ◽  
Yan Wei ◽  
Shaobo Wang ◽  
Jianye Xu ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Xenograft Model ◽  
Glioma Cells ◽  
Tumor Grade ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Orthotopic Xenograft Model ◽  
High Expression Group

Abstract Background: Ribosomal Protein S27-Like is an evolutionarily conserved ribosomal protein and the role of RPS27L influencing the malignance of several cancers has been reported. However, its effects on glioma were still unknown. This investigation aims to characterize the clinical significance and the biological functions of RPS27L in gliomas.Methods: TCGA databases were explored to analyze the correlation between RPS27L expression and the clinical characteristics of glioma patients. Immunohistochemical staining was performed on glioma cases and normal brain tissues. The function of RPS27L in glioma was further explored using U87MG and A172 cell lines and a orthotopic xenograft model of nude mice.Results: Data obtained from TCGA database showed higher expression of RPS27L in glioma than normal, and the overall survival was lower in the high expression group. Immunohistochemistry showed the expression levels of RPS27L were increased with the tumor grade rising in gliomas. Functional assays showed knockdown of RPS27L inhibited proliferation, cell cycle transition, migration and invasion, while promoted apoptosis. Data of western blot indicated that knockdown of RPS27L increased the level of p21，Bax and Cleaved Caspase-3 while decreased the level of CDK4, cyclinD1, cyclinE1, Bcl-2 and MMP2, MMP9 in glioma cells. In vivo, the growth of orthotopic glioma xenografts was suppressed by expression of RPS27L shRNA, and the tumors with RPS27L shRNA showed less aggressiveness and reduced expression of Ki67, Bcl-2 and MMP2. Conclusions: RPS27L is overexpressed in glioma cells. Knockdown of RPS27L could inhibit the proliferation, migration and invasion while promote apoptosis of glioma cells in vitro and in vivo. RPS27L might be a potential prognostic biomarker and possible target for future therapy in glioma.

scholarly journals Long noncoding RNA PVT1 promoted gallbladder cancer proliferation by epigenetically suppressing miR-18b-5p via DNA methylation

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Longyang Jin ◽  
Qiang Cai ◽  
Shouhua Wang ◽  
Shuqing Wang ◽  
Jiandong Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gallbladder Cancer ◽  
Noncoding Rna ◽  
Biliary Tree ◽  
Cancer Proliferation ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Proliferation In Vitro

Abstract Gallbladder cancer (GBC) accounts for 85–90% malignancies of the biliary tree worldwide. Considerable evidence has demonstrated that dysregulation of lncRNAs is involved in the progression of cancer. LncRNA PVT1 has been reported to play important roles in various cancers, but its role in gallbladder cancer remains unknown. In the present study, we found that PVT1 was upregulated in GBC tissues and cells, and its upregulation was related with poor prognosis in GBC patients. PVT1 promoted GBC cells proliferation in vitro and in vivo. Mechanistically, PVT1 recruited DNMT1 via EZH2 to the miR-18b-5p DNA promoter and suppressed the transcription of miR-18b-5p through DNA methylation. Moreover, HIF1A was proved to be the downstream target gene of miR-18b-5p and PVT1 regulated GBC cells proliferation via HIF1A. In conclusion, our studies clarified the PVT1/miR-18b-5p/HIF1A regulation axis and indicated that PVT1 could be a potential therapeutic target for GBC.

Sign in / Sign up

Export Citation Format

Share Document