scholarly journals Double-targeting CDCA8 and E2F1 inhibits the growth and migration of malignant glioma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoxiong Wang ◽  
Heping Wang ◽  
Jiajun Xu ◽  
Xu Hou ◽  
Haoqiang Zhan ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
High Grade Glioma ◽  
Poor Overall Survival ◽  
Survival Prognosis ◽  
Who Grade ◽  
And Migration

AbstractHigh-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated 8 (CDCA8) has been well known as a cell cycle regulator and tumor promotor in various malignant tumors. However, its biological role in glioma still remains unclear. Our results showed that high level of CDCA8 was significantly correlated with advanced WHO grade and poor overall survival and disease-free survival prognosis. In vitro and in vivo investigations demonstrated that CDCA8 promoted the glioma malignancy by promoting cell proliferation, cell migration, and inhibiting cell apoptosis. Moreover, we found its synergetic biological protein—E2F1 by the gene microarray chip. In this study, we revealed that CDCA8 synergized with E2F1 facilitated the proliferation and migration of glioma. In conclusion, our study provides a novel promising therapeutic targets and prognostic biomarkers for malignant glioma treatment.

scholarly journals Nujiangexanthone A Inhibits Hepatocellular Carcinoma Metastasis via Down Regulation of Cofilin 1

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Zhang ◽  
Zongtao Chai ◽  
Siyuan Kong ◽  
Jiling Feng ◽  
Man Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
Mechanism Study ◽  
Down Regulation ◽  
Free Survival ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor prognosis. High expression level of cofilin 1 (CFL1) has been found in many types of cancers. However, the role of CFL1 in HCC hasn’t been known clearly. Here, we found that CFL1 was up regulated in human HCC and significantly associated with both overall survival and disease-free survival in HCC patients. Nujiangexanthone A (NJXA), the caged xanthones, isolated from gamboge plants decreased the expression of CFL1, which also inhibited the migration, invasion and metastasis of HCC cells in vitro and in vivo. Down regulation of CFL1 inhibited aggressiveness of HCC cells, which mimicked the effect of NJXA. Mechanism study indicated that, knockdown of CFL1 or treatment with NJXA increased the level of F-actin and disturbed the balance between F-actin and G-actin. In conclusion, our findings reveal the role of CFL1 in HCC metastasis through the CFL1/F-actin axis, and suggest that CFL1 may be a potential prognostic marker and a new therapeutic target. NJXA can effectively inhibit the metastasis of HCC cells by down regulating the expression of CFL1, which indicates the potential of NJXA for preventing metastasis in HCC.

scholarly journals Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1478
Author(s):  
Huiyuan Zhang ◽  
Lin Qi ◽  
Yuchen Du ◽  
L. Frank Huang ◽  
Frank K. Braun ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mouse Models ◽  
Primary Tumor ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
World Health ◽  
Who Grade ◽  
Orthotopic Xenograft

Background. Meningiomas constitute one-third of all primary brain tumors. Although typically benign, about 20% of these tumors recur despite surgery and radiation, and may ultimately prove fatal. There are currently no effective chemotherapies for meningioma. We, therefore, set out to develop patient-derived orthotopic xenograft (PDOX) mouse models of human meningioma using tumor. Method. Of nine patients, four had World Health Organization (WHO) grade I tumors, five had WHO grade II tumors, and in this second group two patients also had recurrent (WHO grade III) meningioma. We also classified the tumors according to our recently developed molecular classification system (Types A, B, and C, with C being the most aggressive). We transplanted all 11 surgical samples into the skull base of immunodeficient (SCID) mice. Only the primary and recurrent tumor cells from one patient—both molecular Type C, despite being WHO grades II and III, respectively—led to the formation of meningioma in the resulting mouse models. We characterized the xenografts by histopathology and RNA-seq and compared them with the original tumors. We performed an in vitro drug screen using 60 anti-cancer drugs followed by in vivo validation. Results. The PDOX models established from the primary and recurrent tumors from patient K29 (K29P-PDOX and K29R-PDOX, respectively) replicated the histopathology and key gene expression profiles of the original samples. Although these xenografts could not be subtransplanted, the cryopreserved primary tumor cells were able to reliably generate PDOX tumors. Drug screening in K29P and K29R tumor cell lines revealed eight compounds that were active on both tumors, including three histone deacetylase (HDAC) inhibitors. We tested the HDAC inhibitor Panobinostat in K29R-PDOX mice, and it significantly prolonged mouse survival (p < 0.05) by inducing histone H3 acetylation and apoptosis. Conclusion. Meningiomas are not very amenable to PDOX modeling, for reasons that remain unclear. Yet at least some of the most malignant tumors can be modeled, and cryopreserved primary tumor cells can create large panels of tumors that can be used for preclinical drug testing.

scholarly journals microRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract BackgroundIncreasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. MethodsWe carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.ResultsThis study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusionour study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

scholarly journals MicroRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract Background: Increasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. Methods: We carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.Results: This study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusion: our study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

Prognostic value of Mortalin correlates with roles in epithelial–mesenchymal transition and angiogenesis in lung adenocarcinoma

2021 ◽  
Author(s):  
Ziqi Meng ◽  
Rui Zhang ◽  
Xuwei Wu ◽  
Meihua Zhang ◽  
Songnan Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Phenotype ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
In Vivo Experiments ◽  
And Migration

Abstract Mortalin is involved in the malignant phenotype of many cancers. However, the specific molecular mechanisms involving Mortalin in lung adenocarcinoma remain unclear. In this study, we showed that both Mortalin mRNA and protein are overexpressed in lung adenocarcinoma. In addition, Mortalin overexpression was positively-correlated with poor overall survival. In vitro experiments showed that Mortalin silencing inhibited the proliferation, colony formation, and migration abilities of A549 and H1299 cells. Mortalin promotes EMT progression, angiogenesis, and tumor progression by activating the Wnt/β-catenin signaling pathway In vivo experiments further confirmed that Mortalin promoted malignant progression of lung adenocarcinoma. Taken together, our data suggest that Mortalin represents an attractive prognostic marker and therapeutic target in lung adenocarcinoma patients.

scholarly journals Knockdown of DIAPH3 Inhibits the Proliferation of Cervical Cancer Cells through Inactivating mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Linling Wan ◽  
Jiamin Zhu ◽  
Qunying Wu
Keyword(s):  
Cervical Cancer ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Poor Overall Survival ◽  
Western Blot Assay ◽  
Incidence And Mortality

Cervical cancer (CC) ranks fourth for both incidence and mortality among females in worldwide. Therefore, it is urgent to explore new therapeutic and diagnostic targets for cervical cancer. Diaphanous-related formin 3 (DIAPH3) has been identified to play crucial roles in many malignant tumors. But its function and potential mechanism in CC remain largely unknown. In our study, DIAPH3 was frequently upregulated in CC tissue samples and increased expression of DIAPH3 was associated with poor overall survival according to several databases. Through in vitro and in vivo experiments, we found that decreased expression levels of DIAPH3 significantly inhibited the progression of CC. The GSEA analysis and western blot assay indicated that DIAPH3 was associated with the mTOR signaling pathway. The univariate and multivariate Cox analysis indicated that DIAPH3 was an independent prognosis risk factor in TCGA-CESC. And we confirmed that DIAPH3 expression was clearly related to tumor immune infiltrating cells (TIICs) by the analysis of CIBERSORT and TIMER databases. Taken together, we revealed that DIAPH3 plays as an oncogene through mTOR signaling pathway and DIAPH3 might be a potential prognostic biomarker in CC.

scholarly journals CENPU Promotes Growth and Metastasis in Nasopharyngeal Carcinoma by Inhibiting DUSP6

2021 ◽  
Author(s):  
Cheng Lin ◽  
Jingfeng Zong ◽  
Yun Xu ◽  
Jianji Pan ◽  
Meifang Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Nasopharyngeal Carcinoma ◽  
Gene Chip ◽  
Signal Pathways ◽  
Poor Overall Survival ◽  
Migration Assay ◽  
And Migration ◽  
Chip Analysis

Abstract Background: Centromere protein U (CENPU), a centromere component, is key for mitosis and involved in the carcinogenesis of cancers. The role and mechanisms of CENPU in nasopharyngeal carcinoma (NPC) has not been described. Methods: CENPU expression in NPC cells and tissues was evaluated by RT-PCR and western blotting. Clinical significance of CENPU was evaluated by Immunohistochemistry. Biological functions of CENPU were evaluated by cell growth assay, colony formation assay, apoptosis assay, migration assay and invasion assays. Xenograft growth and lung metastasis model were conducted to investigate the effect of CENPU in vivo. Gene chip analysis, Ingenuity Pathway Analysis (IPA), and co-immunoprecipitation (Co-IP) experiments were used to explore the mechanisms of CENPU in NPC.Results: CENPU was highly expressed in NPC cells and samples. Patients with CENPU positive expression were closely associated with poor overall survival. Knockdown of CENPU inhibited proliferation and migration in vitro and in vivo in NPC. Gene chip analysis and IPA suggested that differentially expressed genes (DEGs) were significantly enriched in cancer and functions, including cellular movement, cellular development, cell growth and death, and proliferation when CENPU was downregulated. Dual specificity phosphatase 6 (DUSP6) was one of the DEGs and significantly decreased in NPC samples, and inversely correlated with expression with CENPU. Mechanism studies confirmed that CENPU increased the activation of ERK1/2 and p38 signal pathways by suppressing the expression of DUSP6. Therefore, our results suggested that CENPU might act as an oncogene in NPC and promote the development of NPC via inhibition of DUSP6, resulting in the inactivation of Erk1/2 and p38 pathways. Conclusions: CENPU facilitated cell proliferation and invasion by interacting with DUSP6. CENPU might be a promising prognostic biomarker and a potential target for NPC therapy.

scholarly journals CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiang Feng ◽  
Dongkui Xu ◽  
Mingyao Zhou ◽  
Zijian Wu ◽  
Zhiyuan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colony Formation ◽  
Malignant Tumors ◽  
Cell Model ◽  
Downstream Signaling ◽  
Regulatory Effects ◽  
And Migration ◽  
Related Proteins

Abstract Background Nowadays, colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors worldwide, the incidence rate of which is still increasing year by year. Herein, the objective of this study is to investigate whether CDC42EP3 has regulatory effects in CRC. Methods First, CDC42EP3 knockdown cell model based on HCT116 and RKO cell lines was successfully constructed, which was further used for constructing mouse xenotransplantation models. Importantly, effects of CDC42EP3 knockdown on proliferation, colony formation, apoptosis, and migration of CRC were accessed by MTT assay, EdU staining assay, colony formation assay, Flow cytometry, and Transwell assay. Results As the results, we showed that CDC42EP3 was significantly upregulated in CRC, and its high expression was associated with tumor progression. Furthermore, knockdown of CDC42EP3 could inhibit proliferation, colony formation and migration, and promote apoptosis of CRC cells in vitro. In vivo results further confirmed knockdown of CDC42EP3 attenuated tumor growth in CRC. Interestingly, the regulation of CRC by CDC42EP3 involved not only the change of a variety of apoptosis-related proteins, but also the regulation of downstream signaling pathway. Conclusion In conclusion, the role of CDC42EP3 in CRC was clarified and showed its potential as a target of innovative therapeutic approaches for CRC.

Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

2019 ◽  
Vol 70 (2) ◽  
pp. 718-720
Author(s):  
Lucia Corina Dima-Cozma ◽  
Sebastian Cozma ◽  
Delia Hinganu ◽  
Cristina Mihaela Ghiciuc ◽  
Florin Mitu
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinases ◽  
Cholesterol Synthesis ◽  
Balloon Dilation ◽  
Aortic Aneurysms ◽  
Arterial Lesions ◽  
Smooth Muscle Cell Migration ◽  
And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

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