scholarly journals MAGE-C2/CT10 promotes growth and metastasis through upregulating c-Myc expression in prostate cancer

2020 ◽  
Author(s):  
Jun Qiu ◽  
Bei Yang
Keyword(s):  
Prostate Cancer ◽  
Regulatory Mechanism ◽  
Migration And Invasion ◽  
The Third ◽  
In Vivo Assays ◽  
Significant Homology ◽  
Tumor Growth And Metastasis ◽  
Significant Therapeutic Effect

AbstractProstate cancer (PC) is the most common reproductive cancer in men and the third leading cause of cancer death among men worldwide. Recently targeted therapy showed a significant therapeutic effect on PC, whereas finding more PC therapeutic target is still urgently needed. Melanoma-associated antigen-encoding C2 (MAGE-C2/CT10), which have significant homology with the MAGE-C1/CT-7 gene, was known to be involved in the development of a variety of tumors. However, the role and mechanism of MAGE-C2/CT10 in prostate cancer remains unclear. Herein, we found the high levels of MAGE-C2/CT10 in highly metastatic prostate cancer. Our findings confirmed that the depletion of MAGE-C2/CT10 suppressed the growth of PC cells, and restrained PC cell migration and invasion in vitro. We noticed MAGE-C2/CT10 could stimulate c-Myc expression via FBP1, and further contributed to PC cell proliferation and motility. Performing in vivo assays, we demonstrated MAGE-C2/CT10 promoted tumor growth and metastasis of PC cells in mice. Collectively, we found the abnormal expression of MAGE-C2/CT10 in PC, and revealed the regulatory mechanism underlying MAGE-C2/CT10 promoting PC progression and metastasis.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

scholarly journals Scorpion inhibits epithelial–mesenchymal transition and metastasis of hepatocellular carcinoma

2018 ◽  
Vol 243 (7) ◽  
pp. 645-654 ◽  
Author(s):  
Yi-Quan Yan ◽  
Juan Xie ◽  
Jing-Fu Wang ◽  
Zhao-Feng Shi ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Unfavorable Clinical Outcome ◽  
Metastasis Models ◽  
Tumor Growth And Metastasis

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial–mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

scholarly journals LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Enhui Ma ◽  
Qianqian Wang ◽  
Jinhua Li ◽  
Xinqi Zhang ◽  
Zhenjia Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Novel Target

Abstract Background Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet. Methods RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified. Results LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression. Conclusions LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.

scholarly journals Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Tao Chen ◽  
Fu-Kuan Zhong
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

scholarly journals lncRNA H19 binds VGF and promotes pNEN progression via PI3K/AKT/CREB signaling

2019 ◽  
Vol 26 (7) ◽  
pp. 643-658 ◽  
Author(s):  
Meng Ji ◽  
Yanli Yao ◽  
Anan Liu ◽  
Ligang Shi ◽  
Danlei Chen ◽  
...  
Keyword(s):  
Migration And Invasion ◽  
Neuroendocrine Neoplasms ◽  
Endocrine Tumors ◽  
Rna Seq ◽  
Rna Immunoprecipitation ◽  
Poor Differentiation ◽  
Tumor Growth And Metastasis

Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain undefined. Microarray analysis was conducted to identify the differentially expressed lncRNAs in pNENs. H19 expression was analyzed in 39 paired pNEN tissues by qPCR. The biological role of H19 was determined by functional experiments. RNA pulldown, mass spectroscopy and RNA immunoprecipitation were performed to confirm the interaction between H19 and VGF. RNA-seq assays were performed after knockdown H19 or VGF. H19 was significantly upregulated in pNEN tissues with malignant behaviors, and the upregulation predicted poor prognosis in pNENs. In vitro and in vivo data showed that H19 overexpression promoted tumor growth and metastasis, whereas H19 knockdown led to the opposite phenotypes. H19 interacted with VGF, which was significantly upregulated in pNENs, and higher VGF expression was markedly related to poor differentiation and advanced stage. Furthermore, VGF was downregulated when H19 was knocked down, and VGF promoted cell proliferation, migration and invasion. Mechanistic investigations revealed that H19 activated PI3K/AKT/CREB signaling and promoted pNEN progression by interacting with VGF. These findings indicate that H19 is a promising prognostic factor in pNENs with malignant behaviors and functions as an oncogene via the VGF-mediated PI3K/AKT/CREB pathway. In addition, our study implies that VGF may also serve as a candidate prognostic biomarker and therapeutic target in pNENs.

scholarly journals LncRNA CASC11 Promotes Hepatocellular Carcinoma Progression via Upregulation of UBE2T in a m6A-Dependent Manner

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Chen ◽  
Meijun Li ◽  
Liang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cancer Susceptibility ◽  
Underlying Mechanism ◽  
Epigenetic Mechanism ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Tumor Growth And Metastasis

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide. Besides, it has been revealed that long non-coding RNA (LncRNA) cancer susceptibility candidate 11 (CASC11) is involved in cancer progression. However, the functional role and underlying mechanism of CASC11 in HCC remains largely unknown. In this context, here, it was found that CASC11 was upregulated in HCC tissues and associated with tumor grades, metastasis, and prognosis of HCC patients. Functionally, CASC11 facilitated HCC cell proliferation, migration, and invasion in vitro, and enhanced tumor growth and metastasis in vivo. Mechanistically, CASC11 associated with and stabilized Ubiquitin-conjugating enzyme E2T (UBE2T) mRNA. To be specific, it decreased UBE2T N6-methyladenosine (m6A) level via recruiting ALKBH5. Moreover, CASC11 inhibited the association between UBE2T mRNA and m6A reader protein YTHDF2. Taken together, our findings demonstrate the epigenetic mechanism of CASC11 in the regulation of UBE2T expression and possibly provide a novel therapeutic target for HCC treatment.

scholarly journals Long Non-Coding RNA NEAT1 Promotes HCC Progression via PKM2 and Exosome-Mediated Transfer

2021 ◽  
Author(s):  
Junping Pan ◽  
Yingzhe Hu ◽  
Chenlu Yuan ◽  
Yafu Wu ◽  
Xinhua Zhu
Keyword(s):  
Malignant Tumors ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Mouse Xenograft Model ◽  
Rna Immunoprecipitation ◽  
Tumor Growth And Metastasis ◽  
Lncrna Neat1 ◽  
Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality and poor prognosis. Long non-coding RNAs NEAT1 (lncRNA NEAT1) have been found to play an important role in HCC progression. However, the role and potential molecular mechanism of lncRNA NEAT1 in HCC remain largely unclear. Methods The role of lncRNA NEAT1 both in vitro and in vivo was investigated, with RNA pull-down and RNA immunoprecipitation (RIP) assays being performed to determine the interaction among NEAT1 and FOXO3 and PKM2. In addition, HCC cells were treated with exosomes derived from NEAT1-overexpressing HCC cells, and then cell proliferation, migration and invasion were assessed using in vitro assays. Results In this study, overexpression of NEAT1 promoted the proliferation, migration and invasion of HCC cells, whereas NEAT1 knockdown exhibited the opposite effects. Mechanistically, NEAT1 was found to recruit transcription factor FOXO3 to PKM2 promoter region and upregulate PKM2 expression. Meanwhile, overexpression of NEAT1 increased tumor growth and metastasis in a mouse xenograft model of HCC in vivo via upregulation of PKM2. Furthermore, overexpression of NEAT1 promoted exosome release from HCC cells. Exosomes secreted from NEAT1-overexpressing HCC cells promoted the proliferation, migration and invasion of HCC cells. Conclusion We found that NEAT1 could promote HCC progression via upregulation of PKM2 and exosome-mediated transfer. These data indicated that NEAT1 may be a therapeutic target in HCC.

scholarly journals LncRNA RNCR3 Promotes the Progression of HCC by Activating the Akt/GSK3β Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qi Xie ◽  
Tongfa Ju ◽  
Chunhua Zhou ◽  
Lulu Zhai ◽  
Ho Lin
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Promote Cell Proliferation ◽  
Qrt Pcr ◽  
In Vivo Experiments ◽  
Tumor Number ◽  
Tumor Growth And Metastasis

Objective. To explore the potential biological roles of long noncoding RNA (lncRNA) RNCR3 in human hepatocellular carcinoma (HCC). Methods. First, the expression of RNCR3 was detected by qRT-PCR. Then, in vitro experiments were performed to investigate the effects of RNCR3 on the proliferation, cell cycle, migration, and invasion of HCC cells, while the effects of RNCR3 on HCC tumor growth and metastasis were investigated using in vivo experiments. Finally, western blot was used to study the activation of the Akt/GSK3β signaling pathway. Results. RNCR3 was highly expressed in both HCC tissues and cells, and the expression of RNCR3 was closely related to tumor size, tumor number, TNM stage, and overall survival time. In vitro, RNCR3 served as an oncogene to promote cell proliferation, migration, and invasion, and in vivo, RNCR3 promoted the growth and metastasis of HCC tumors. In terms of mechanism, RNCR3 induced the phosphorylation of Akt (thr308 and ser473) and GSK3β (ser9) but decreased the expression of GSK3β, which activated the Akt/GSK3β signaling pathway. Conclusion. The high expression of lncRNA RNCR3 in HCC can promote the proliferation, migration, invasion, growth, and metastasis of HCC by activating the NF-κB signaling pathway.

scholarly journals Aberrant KIF20A Expression Is Associated with Adverse Clinical Outcome and Promotes Tumor Progression in Prostate Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zheng Zhang ◽  
Ciman Chai ◽  
Tianyu Shen ◽  
Xiaoqing Li ◽  
Junpeng Ji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Protein Level ◽  
Bioinformatics Analysis ◽  
Prostate Cancer Cell ◽  
Migration And Invasion ◽  
Normal Prostate ◽  
Normal Prostate Tissue

Purpose. KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. Methods. Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. Results. KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. Conclusions. Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.

scholarly journals Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo

2010 ◽  
Vol 17 (2) ◽  
pp. 481-493 ◽  
Author(s):  
Lei Gu ◽  
Paraskevi Vogiatzi ◽  
Martin Puhr ◽  
Ayush Dagvadorj ◽  
Jacqueline Lutz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Human Prostate ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Metastatic Behavior

There are no effective therapies for disseminated prostate cancer. Constitutive activation of Stat5 in prostate cancer is associated with cancer lesions of high histological grade. We have shown that Stat5 is activated in 61% of distant metastases of clinical prostate cancer. Active Stat5 increased metastases formation of prostate cancer cells in nude mice by 11-fold in an experimental metastases assay. Active Stat5 promoted migration and invasion of prostate cancer cells, and induced rearrangement of the microtubule network. Active Stat5 expression was associated with decreased cell surface E-cadherin levels, while heterotypic adhesion of prostate cancer cells to endothelial cells was stimulated by active Stat5. Activation of Stat5 and Stat5-induced binding of prostate cancer cells to endothelial cells were decreased by inhibition of Src but not of Jak2. Gene expression profiling indicated that 21% of Stat5-regulated genes in prostate cancer cells were related to metastases, while 7.9% were related to proliferation and 3.9% to apoptosis. The work presented here provides the first evidence of Stat5 involvement in the induction of metastatic behavior of human prostate cancer cells in vitro and in vivo. Stat5 may provide a therapeutic target protein for disseminated prostate cancer.

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