SAHA modulates cell proliferation, colony forming and epithelial-mesenchymal transition in CCA cells

2018 ◽  
Vol 44 (1) ◽  
pp. 70-77
Author(s):  
Gülden Başkol ◽  
Merve Özel ◽  
Çiğdem Uçar ◽  
Büşra Nur Doğru ◽  
Esra Hilal Yüksek ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Protein Level ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Regimen ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Cholangiocarcinoma Cell ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Therapeutic options for advanced cholangiocarcinoma (CCA) are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor. So that, we planned to investigate epigenetic regulation of epithelial-mesenchymal transition (EMT) in cholangiocarcinoma cell line by applying Suberoylanilide hydroxamic acid (SAHA). We studied the effect of SAHA on cell proliferation, colony forming, migration and protein level of E-cadherin (E-cad) as an epithelial EMT marker, N-cadherin (N-cad) and Vimentin (Vim), as a mesenchymal markers of EMT, in human CCA cell line. Materials and methods Cell proliferation and migration measurements were performed by flow cytometry and wound healing assay, respectively. E-cad, N-cad and Vim protein levels were determined by Western blot analysis. Results It was found that SAHA significantly inhibits cell viability, proliferation and migration of TFK-1 cells, accompanied by reversing of EMT markers. SAHA, upregulated protein level of E-cad, while downregulated the protein levels of N-cad and Vimentin. Conclusions SAHA treatment may bebeneficial for CCA patients and SAHA might be a potential therapeutic agent for the treatment of CCA. However, future studies are needed to evaluate the clinical applicability of SAHA as a part of the chemotherapeutic regimen for CCA.

scholarly journals Tumor-Suppressive Function of lncRNA-MEG3 in Glioma Cells by Regulating miR-6088/SMARCB1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Gong ◽  
Meng-Yi Huang
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Favorable Effect ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
And Migration ◽  
Proliferation And Migration ◽  
Glioma Progression

Objective. Mounting evidence has elaborated the implication of long noncoding RNAs (lncRNAs) in tumorigenesis of several cancers, including glioma. However, little was known about the mechanism of lncRNA maternally expressed gene 3 (MEG3) in the development and progression of glioma. This work is designed to explore the effect of MEG3 on glioma progression and its possible mechanism. Methods. Expressions of lncRNA-MEG3 and SMARCB1 were detected in human glioblastoma U87 and U251 cell lines. Gain and loss of function of MEG3 or/and miR-6088 was performed in U87 and U251 cells to observe its effect on cell proliferation and migration as well as on epithelial-mesenchymal transition (EMT) related markers. Luciferase reporter gene assay was employed to inspect the interactions among MEG3, miR-6088, and SMARCB1. Results. MEG3 and SMARCB1 expressions were downregulated in glioma cells. Transfection of pcDNA3.1-MEG3 or pcDNA3.1-SMARCB1 plasmids could clearly block cell proliferation, migration, and EMT progression. MEG3 functions as a sponge for miR-6088, while SMARCB1 is a downstream protein of miR-6088. Transfection of miR-6088 mimic or si-SMARCB1 could obviously reverse the favorable effect of pcDNA3.1-MEG3 on glioma progression. Conclusion. Collectively, the evidence in this study indicated that MEG3 was downregulated in glioma cells and inhibited proliferation and migration of glioma cells via regulating miR-6088/SMARCB1 axis.

scholarly journals Purinergic P2Y2 and P2X4 Receptors Are Involved in the Epithelial-Mesenchymal Transition and Metastatic Potential of Gastric Cancer Derived Cell Lines

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1234
Author(s):  
Mauricio Reyna-Jeldes ◽  
Erwin De la Fuente-Ortega ◽  
Daniela Cerda ◽  
Erandi Velázquez-Miranda ◽  
Katherine Pinto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Purinergic Signaling ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
P2x4 Receptors ◽  
And Migration ◽  
Proliferation And Migration

Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells.

scholarly journals Overexpression of carboxypeptidase X M14 family member 2 predicts an unfavorable prognosis and promotes proliferation and migration of osteosarcoma

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Zhao ◽  
Ronghang Li ◽  
Qian Wang ◽  
Minfei Wu ◽  
Yanbing Wang
Keyword(s):  
Cell Proliferation ◽  
Family Member ◽  
Western Blotting ◽  
Epithelial Mesenchymal Transition ◽  
Osteosarcoma Cells ◽  
Osteoblast Cells ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human developmental disorders. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. Currently, the clinical relevance and function of CPXM2 in human osteosarcoma were investigated. Materials and methods The expression of CPXM2 in osteosarcoma cell lines and tissues were explored by immunohistochemistry and western blotting assays. A eukaryotic expression plasmid was transfected into fetal osteoblast cells to overexpress CPXM2 and the endogenous CPXM2 in osteosarcoma cells was silenced through an RNA interference (RNAi) method transfection. These transfections were validated via western blotting, and the expression levels of several key molecules involved in the epithelial mesenchymal transition was also determined via western blotting. The expression levels of CPXM2 in a fetal osteoblast cell line with CPXM2 overexpressing and an osteosarcoma CPXM2-knockout cell line was confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence. The malignant phenotype of osteosarcoma cells was indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. Results We found that CPXM2 was overexpressed in osteosarcoma and that the overexpression was associated with an unfavorable prognosis and tumor node metastasis staging. The knockdown of CPXM2 in cultured osteosarcoma cells significantly impeded cell proliferation and migration. In addition, the upregulation of CPXM2 in fetal osteoblast cells significantly promoted cell proliferation and migration. Besides, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition (EMT) were regulated by CPXM2. Conclusion Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in osteosarcoma.

scholarly journals ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Huojian Shen ◽  
Hongyi Zhu ◽  
Yuanwen Chen ◽  
Zhiyong Shen ◽  
Weiqing Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
Novel Target ◽  
And Migration ◽  
Proliferation And Migration

AbstractGastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.

scholarly journals Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial–Mesenchymal Transition Pathways

2021 ◽  
Vol 8 ◽  
Author(s):  
Md Zahirul Islam Khan ◽  
Helen Ka Wai Law
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Susceptibility ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
Hct 116 ◽  
And Migration ◽  
Proliferation And Migration

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide. Many recent studies have demonstrated that different long non-coding RNAs (lncRNAs) are involved in the initiation, advancement, and metastasis of many cancers including CRC. Cancer susceptibility candidate 9 (CASC9) is an lncRNA that has been reported in many cancers, but its role in CRC is poorly understood. In this study, we aimed to examine the expression of CASC9 in CRC cell lines and to determine the mechanism of action of CASC9 in CRC carcinogenesis.MethodsThe expression of CASC9 in CRC tissues was compared with normal samples from publicly available datasets in The Cancer Genome Atlas (TCGA) and The Encyclopedia of RNA Interactomes (ENCORI). CASC9 expression was further verified in four CRC cell lines (DLD1, HT-29, SW480, and HCT-116) and normal colorectal cell line (CCD-112CoN) by real-time quantitative polymerase chain reaction (RT-qPCR). After gene silencing in HCT-116 and SW480, Cell Counting Kit-8 assay, clonogenic assay, and wound healing assay were performed to evaluate cell proliferation, viability, and migration index of cells. Western blotting was used to explore the key pathways involved.ResultsCASC9 was significantly upregulated as analyzed from both public datasets TCGA and ENCORI where its overexpression was associated with poor survival of CRC patients. Similarly, CASC9 was significantly overexpressed in the CRC cell lines compared with normal cells studied. The silencing of CASC9 in HCT-116 and SW480 attenuated cell proliferation and migration significantly. Furthermore, pathways investigations showed that silencing of CASC9 significantly induced autophagy, promoted AMP-activated protein kinase (AMPK) phosphorylation, inhibited mTOR and AKT signaling pathways, and altered epithelial–mesenchymal transition (EMT) marker protein expression.ConclusionWe demonstrated that silencing of CASC9 contributes to the reduced CRC cell proliferation and migration by regulating autophagy and AKT/mTOR/EMT signaling. Therefore, CASC9 plays an important role in carcinogenesis, and its expression may act as a prognostic biomarker and a potential therapeutic target of CRC management.

scholarly journals CircACAP2 promotes cell proliferation and migration in lung adenocarcinoma via LASP1-mediated TGF‐β/Smad3 pathway

2021 ◽  
Author(s):  
Jianyu Xu ◽  
Jianli Ma ◽  
Bixi Guan ◽  
Jian Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Regulatory Mechanism ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Lung adenocarcinoma (LUAD), a common malignant tumor, has led to a great number of deaths around the world. Circular RNAs (circRNAs) have been certified as essential players in the progression of diverse cancers. CircRNA ACAP2 (hsa_circ_0068568) is an oncogene in several cancers. However, the role of circACAP2 in LUAD remains unknown. This study revealed that the expression of circACAP2 was significantly elevated in LUAD tissues and cell lines, especially in the tissues of LUAD patients at advanced stage. Additionally, circACAP2 enhanced cell proliferation, migration, invasion abilities and epithelial-mesenchymal transition (EMT) process in LUAD. Moreover, miR-342-3p interacted with circACAP2 in LUAD cells. Importantly, we found that miR-342-3p targeted LIM and SH3 protein 1 (LASP1), and circACAP2 positively regulated LASP1 expression by competing for miR-342-3p in LUAD. Further, it was confirmed that circACAP2 promoted the malignant behaviors and stimulated the activation of TGF-β/Smad3 pathway in LUAD by modulating the miR-342-3p/LASP1 axis. To conclude, the molecular regulatory mechanism of circACAP2 in LUAD was under discussion in the current study. The findings revealed that circACAP2 facilitated malignant phenotypes in LUAD via the activation of the TGF‐β/Smad3 pathway.

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