scholarly journals Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259075
Author(s):  
Pirawan Poosekeaw ◽  
Chawalit Pairojkul ◽  
Banchob Sripa ◽  
Prakasit Sa Ngiamwibool ◽  
Sitthichai Iamsaard ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Tnm Staging ◽  
Clinicopathological Parameters ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Formalin Fixed Paraffin Embedded ◽  
T Classification

Cholangiocarcinoma (CCA) is a group of heterogenous malignancies arising from bile duct epithelium with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein XB130 (AFAP1L2) is a critical biological determinant of CCA outcome. XB130 expression levels were investigated in four CCA cell lines compared to an immortalized cholangiocyte cell line by Western blotting. Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects of reduced XB130 expression on cell proliferation, migration, and invasion by MTT, transwell migration and cell invasion assay. The immunohistochemical quantification of XB130 levels were performed in surgically resected formalin-fixed, paraffin-embedded specimens obtained from 151 CCA patients. The relationship between XB130 expression and the clinicopathological parameters of CCA patients were analyzed. Our results showed that XB130 was highly expressed in KKU-213A cell line. Knockdown of XB130 using siRNA significantly decreased the proliferation, migration, and invasion properties of KKU-213A cells through the inhibition of PI3K/Akt pathway, suggesting that XB130 plays an important role in CCA progression. Moreover, elevated XB130 expression levels were positive relationship with lymphovascular space invasion (LVSI), intrahepatic type of CCA, high TNM staging (stage III, IV), high T classification (T3, T4), and lymph node metastasis. We provide the first evidence that the overexpression of XB130 is associated with tumorigenic properties of CCA cells, leading to CCA progression with aggressive clinical outcomes.

scholarly journals ANLN Promotes Cell Migration and Invasion Through RhoA-ROCK Signaling in Cervical Cancer

2021 ◽  
Author(s):  
Congzhe Hou ◽  
Zhen Liang ◽  
Yongxia Yang ◽  
Yunhai Yu ◽  
Tingting Liang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Stress Fiber ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Actin Stress Fiber ◽  
Western Blots ◽  
Expression Levels ◽  
Cell Migration And Invasion

IntroductionAnillin actin binding protein (ANLN) is involved in various human cancers. It is often upregulated in various cancers, including cervical cancer (CC). however, the exact role of ANLN in the modulation of CC and the underlying molecular mechanism remain unknown. In this study, we aimed to investigate the effects of ANLN on the proliferation, migration, and invasion of CC cells, as well as determine the molecular mechanisms underlying these effects.Material and methodsANLN expression levels were analyzed in normal cervical and CC specimens using public databases and tissue samples. The prognosis was determined using TCGA database. Cell proliferation, migration and invasion were measured by Edu assay, wound-healing assay and transwell assay, respectively. Immunofluorescence was used to examined the influence actin stress fiber integrity caused by ANLN inhibition. Western blots were used to measure the protein expression.ResultsANLN expression levels in CC were higher than those in normal tissues, and ANLN overexpression was highly correlated with poor prognosis. ANLN knockdown inhibited CC cell proliferation, migration, and invasion in vitro, while ANLN overexpression exerted an inverse biological phenotype. Immunofluorescence showed that ANLN inhibition could influence actin stress fiber integrity. ANLN expression was positively correlated with ROCK1 and ROCK2 expression in CC. Overexpression of ANLN activated RhoA and upregulated ROCK1 and ROCK2. Furthermore, ROCK1 and ROCK2 expression levels were also impeded by Y27632, which is a specific inhibitor of RhoA. They also weakened the migration and invasion ability in ANLN overexpression HeLa cells.ConclusionsANLN promotes cell migration and invasion through RhoA-ROCK signaling in CC.

scholarly journals Lobaplatin Inhibits Prostate Cancer Proliferation and Migration Through Regulation of BCL2 and BAX

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581985098 ◽  
Author(s):  
Hongwen Cao ◽  
Yigeng Feng ◽  
Lei Chen ◽  
Chao Yu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Cancer Proliferation ◽  
Expression Levels ◽  
And Migration ◽  
Proliferation And Migration

Lobaplatin is a diastereometric mixture of platinum (II) complexes, which contain a 1,2-bis (aminomethyl) cyclobutane stable ligand and lactic acid. Previous studies have showed that lobaplatin plays inhibiting roles in various types of tumors. However, the role of lobaplatin in prostate cancer remains unknown. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell proliferation was detected by cell colony formation assay. Cell migration and invasion were determined by transwell migration and invasion assay. Cell apoptosis was detected by flow cytometry. The messenger RNA and protein expression levels were detected by quantitative real-time polymerase chain reaction and Western blot. Lobaplatin treatment inhibits cell viability, cell proliferation, cell migration, and invasion, while promotes cell apoptosis of prostate cancer cell lines DU145 and PC3. Meanwhile, lobaplatin treatment regulates apoptosis by downregulation of BCL2 expression and upregulation of BAX expression levels. Our study suggests lobaplatin inhibits prostate cancer proliferation and migration through regulation of BCL2 and BAX expression.

scholarly journals Silencing of the TROP2 gene suppresses proliferation and invasion of hepatocellular carcinoma HepG2 cells

2019 ◽  
Vol 47 (3) ◽  
pp. 1319-1329 ◽  
Author(s):  
Jian Zhang ◽  
Hai Ma ◽  
Liu Yang ◽  
Hongchun Yang ◽  
Zhenxing He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Human Trophoblast ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Proliferation And Invasion

Objectives Overexpression of human trophoblast cell surface antigen 2 (Trop2) has been observed in many cancers; however, its roles in proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) remain unclear. Thus, this study aimed to characterize the function of Trop2 in HCC. Methods Trop2 protein expression was detected by immunohistochemistry in HCC tissues. Cell proliferation, apoptosis, and invasion were respectively measured by CCK-8, flow cytometry, Transwell, and wound healing assays. Expression levels of epithelial–mesenchymal transition-related proteins and Trop2 protein in HCC cell lines were detected by western blotting after silencing of the TROP2 gene. Results Trop2 protein was highly expressed in HCC tissues and HCC cell lines. Trop2 mRNA and protein expression levels decreased in HepG2 and HCCLM3 cells after transfection with Trop2 siRNA. Silencing of the TROP2 gene in HepG2 and HCCLM3 cells strongly inhibited cell proliferation and migration, while enhancing cell apoptosis. Investigation of the molecular mechanism revealed that silencing of the TROP2 gene suppressed epithelial–mesenchymal transition of HepG2 and HCCLM3 cells. Conclusions The results of the present study may improve understanding of the role of Trop2 in regulation of cell proliferation and invasion, and may aid in development of novel therapy for HCC.

scholarly journals Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Run-Tian Liu ◽  
Jing-Lin Cao ◽  
Chang-Qing Yan ◽  
Yang Wang ◽  
Cong-Jing An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Line ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Human Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Experimental Group

The present study explored the effect of long non-coding RNA-human ovarian cancer-specific transcript 2 (LncRNA-HOST2) on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma (HCC) cell line SMMC-7721. HCC tissues and adjacent normal tissues from 162 HCC patients were collected. The HCC cell lines were assigned into the control group (regular culture), negative control (NC) group (transfected with siRNA) and experimental group (transfected with Lnc-HOST2 siRNA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of LncRNA-HOST2. Cell proliferation was detected by CCK-8 and colony-forming assays, cell apoptosis by flow cytometry and cell migration by Scratch test. Transwell assay was used to evaluate cell migration and invasion abilities. LncRNA-HOST2 expression in the HCC tissues increased 2–10 times than that in the adjacent normal tissues. Compared with the HL-7702 cell line, LncRNA-HOST2 expression in HepG2, SMMC-7721 and Huh7 cell lines was all up-regulated, but the SMMC-7721 cell had the highest Lnc-HOST2 expression. The LncRNA-HOST2 expression in the experimental group was down-regulated as compared with the control and NC groups. In comparison with the control and NC groups, cloned cells reduced, cell apoptosis increased, clone-forming ability weakened and inhibitory rate of colony formation increased in the experimental group. The cells migrating and penetrating into the transwell chamber were fewer in the experimental group than those in the control and NC groups. The experimental group exhibited slow wound healing and decreased cell migration area after 48 h. These findings indicate that LncRNA-HOST2 can promote cell proliferation, migration and invasion and inhibit cell apoptosis in human HCC cell line SMMC-7721.

scholarly journals CircRNA circPDSS1 promotes bladder cancer by down-regulating miR-16

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Qinnan Yu ◽  
Pei Liu ◽  
Guangye Han ◽  
Xiangdong Xue ◽  
Derong Ma
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Migration Rates ◽  
Urothelial Bladder ◽  
And Migration

Abstract Background: Circular RNA (circRNA) circPDSS1 is a recently identified oncogene in gastric cancer, while its roles in other types of cancer are unknown. We investigated the functions of circPDSS1 in urothelial bladder cancer (UBC). Materials and methods: Seventy-two patients (50 males and 22 females, age 38–69 years, mean: 52.3 ± 6.3 years) with UBC were enrolled in Gansu Provincial People’s Hospital from August 2015 to August 2018. RT-qPCR was used to measure gene expression levels in both biopsies from UBC patients and in vitro cultivated HT-1197 and UMUC3 cells. Cell transfections were performed to analyze gene interactions. Cell proliferation, transwell migration and invasion assays were performed to analyze the effects of transfections on HT-1197 and UMUC3 cell proliferation, migration and invasion, respectively. Results: We found that circPDSS1 was up-regulated in UBC. Expression levels of circPDSS1 were increased with increase in clinical stages. MiR-16 was down-regulated and correlated with circPDSS1 in UBC. Overexpression of circPDSS1 led to down-regulation of miR-16, while miR-16 overexpression failed to significantly affect circPDSS1. Overexpression of circPDSS1 led to increased proliferation, invasion and migration rates of UBC cells. Overexpression of miR-16 not only led to inhibited proliferation, invasion and migration of UBC cells, but also attenuated the effects of circPDSS1 overexpression. Conclusion: Therefore, circRNA circPDSS1 may promote UBC by down-regulating miR-16.

scholarly journals Dysregulation of ANKRD11 Influenced Hematopoisis By Histone Acetylation-Mediated Gene Expression in Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4292-4292
Author(s):  
Youshan Zhao ◽  
Feng Xu ◽  
Juan Guo ◽  
Sida Zhao ◽  
Chunkang Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Histone Acetylation ◽  
Mrna Expression ◽  
Cell Line ◽  
Expression Levels ◽  
Target Sequencing ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mrna Expression Levels

Abstract Background and Object In addition to histone deacetylation, the importance of histone over-acetylation induced oncogene transcription in initiation and progression of myelodysplastic syndrome (MDS) has been proposed recently. Our previous whole-exome sequencing identified a new somatic mutation, ANKRD11, an important factor in histone acetylation regulation. Its roles in MDS pathophysiology need to be clarified. Methods The next generation target sequencing (Including ANKRD11) was carried out in 320 patients with MDS using the MiSeq Benchtop Sequencer. ANKRD11 mRNA expression in bone marrow of MDS was measured by real-time PCR. Loss and gain of function assay were carried out in myeloid cell lines K562, MEG-01£¬or SKM-1 to observe the influence on cell proliferation and differentiation . The levels of histone acetylation at H3 and H4 were detected by Western blot. Results Target sequencing in a cohort of 320 MDS patients identified 14 of ANKRD11 mutations (4.38%, Fig.1), which were confirmed by Sanger sequencing. Meanwhile, no ANKRD11 mutations in 100 normal controls were defined. ANKRD11 mutations occurred frequently in exons 10 and 9. The mRNA expression levels of ANKRD11 were significantly decreased in MDS patients, especially in ANKRD11mutant patients (Fig.2). ANKRD11 knockdown in K562 and MEG-1 resulted in growth inhibition, cell cycle arrest and erythroid/megakaryocytic differentiation retardant. In MDS cell line SKM-1, the arrested differentiation was rescued by over-expression of ANKRD11. Consistent with a role for ANKRD11 in histone acetylation, ANKRD11 KD increased acetylation of histones H3 and H4 at H3K14 and H4K5 and resulted in the upregulation of genes involved in differentiation inhibilation (SOX6, P21, et al). Finally, the ANKRD11 KD-mediated influence on cell proliferation and differentiation were reversed by inhibiting histone acetyltransferase activity. Conclusion Our assay defined that ANKRD11 was a crucial chromatin regulator that suppress histone acetylation and then decrease gene expression during myeloid differentiation, providing a likely explanation for its role in MDS pathogenesis. This study further support histone acetylase inhibitor as a potential treatment in MDS. Figure ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure. ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Figure. The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Disclosures No relevant conflicts of interest to declare.

USP44 hypermethylation promotes cell proliferation and metastasis in breast cancer

2020 ◽  
Author(s):  
Xin Chen ◽  
Xiaotang Wu ◽  
Wen Lei
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Cell Behaviors ◽  
Specific Pcr ◽  
Proliferation And Metastasis ◽  
Induced Apoptosis

Aim: The methylation and expression levels of USP44 in breast cancer were investigated and their effects on tumor cells were researched. Materials & Methods: Bioinformatics was employed to identify the target gene from TCGA database. Sodium bisulfite and decitabine were used for DNA modification and demethylation, and methylation-specific PCR and reverse transcriptase PCR were performed to assess USP44 methylation and expression levels. Tumor cell behaviors were assayed via several in vitro experiments. Results: USP44 was hypermethylated, which caused its poor expression in breast cancer, whereas its overexpression significantly suppressed cancer cell proliferation, migration and invasion and induced apoptosis. Conclusion: USP44 negatively functions in cancer progression upon overexpression, indicating its potential as a therapeutic target for clinical treatment of breast cancer.

scholarly journals Metformin suppresses the proliferation and invasion through NF-kB and MMPs in MCF-7 cell line

2019 ◽  
Vol 45 (3) ◽  
pp. 295-304
Author(s):  
Nail Besli ◽  
Guven Yenmis ◽  
Matem Tunçdemir ◽  
Elif Yaprak Sarac ◽  
Sibel Doğan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cancer Cell Line ◽  
Immunocytochemical Staining ◽  
Breast Adenocarcinoma ◽  
Control Group ◽  
Expression Levels ◽  
Er Positive ◽  
Mcf 7

AbstractObjectiveMCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line.Materials and methodsMCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining.ResultsThe percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05).ConclusionMetformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.

scholarly journals Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bao Liu ◽  
Li Yan ◽  
Yugang Chi ◽  
Yuhan Sun ◽  
Xiaoyu Yang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Tumor Development ◽  
Figo Stage ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Gene Reporter Assay

Abstract Background Abnormally expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC). Methods The relative expression levels of lncRNA AFAP1-AS1, microRNA (miR)-107 and pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA were assessed by quantitative real-time PCR. PDK4, PCNA and cyclin D1 expression levels were determined using Western blot analysis. Bioinformatics analysis and dual-luciferase gene reporter assay were conducted for identifying and validating the binding sequences between AFAP1-AS1 and miR-107, as well as between miR-107 and PDK4. Cell counting kit-8 assay was employed for detecting cell proliferation. Cell migration and invasion abilities were examined using Transwell assays. Results The present study revealed that AFAP1-AS1 expression was elevated in OC cells and tissues. AFAP1-AS1 expression and FIGO stage were positively correlated. AFAP1-AS1 knockdown repressed OC cell proliferation, migration and invasion. AFAP1-AS1 functioned as a sponge of miR-107, and miR-107 reversed the effects of AFAP1-AS1 on OC cells. It was validated that miR-107 was able to bind to PDK4, and AFAP1-AS1 regulated PDK4 expression by competitively binding with miR-107. Additionally, miR-107 modulated OC cell proliferation, migration and invasion via targeting PDK4. Conclusions LncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/PDK4 axis.

XB130 deficiency enhances carcinogen-induced skin tumorigenesis

2019 ◽  
Vol 40 (11) ◽  
pp. 1363-1375 ◽  
Author(s):  
Hae-Ra Cho ◽  
Yingchun Wang ◽  
Xiaohui Bai ◽  
Yun-Yan Xiang ◽  
Christina Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tyrosine Kinases ◽  
Nuclear Factor Kappa B ◽  
Adaptor Protein ◽  
Skin Tumor ◽  
Migration And Invasion ◽  
Wild Type ◽  
Skin Tumorigenesis ◽  
Metalloproteinase 9

AbstractXB130 is an adaptor protein that functions as a mediator of multiple tyrosine kinases important for regulating cell proliferation, survival, migration and invasion. Formerly predicted as an oncogene, alterations of its expression are documented in various human cancers. However, the exact role of XB130 in tumorigenesis is unknown. To address its function in skin tumorigenesis, a two-stage dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA) study was performed on XB130 knockout (KO), heterozygous (HZ) and wild-type (WT) littermate mice. DMBA/TPA-treated XB130 KO and HZ males developed a significantly higher number of epidermal tumors that were notably larger in size than did WT mice. Interestingly, DMBA/TPA-treated female mice did not show any difference in tumor multiplicity regardless of the genotypes. The skin tumor lesions of XB130 KO males were more progressed with an increased frequency of keratoacanthoma. Deficiency of XB130 dramatically increased epidermal tumor cell proliferation. The responses to DMBA and TPA stimuli were also individually investigated to elucidate the mechanistic role of XB130 at different stages of tumorigenesis. DMBA-treated male XB130 KO mice showed compensatory p53-mediated stress response. TPA-treated XB130 KO males demonstrated more skin ulceration with more severe edema, enhanced cell proliferation, accumulation of infiltrating neutrophils and increased production of pro-inflammatory cytokine genes compared with WT mice. Enhanced activities of nuclear factor-kappa B pathway, increased protein expression of metalloproteinase-9 and ERK1/2 phosphorylation were found in these KO mice. These findings demonstrate that XB130 acts as a tumor suppressor in carcinogen-induced skin tumorigenesis that may be mediated through inhibiting inflammation.

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