scholarly journals MicroRNA-93 promotes the tumorigenesis of osteosarcoma by targeting TIMP2

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Hua Zhang ◽  
Jidong Zhang ◽  
Fanrui Meng ◽  
Hanzhong Zhu ◽  
Hongyu Yan ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Primary Bone ◽  
Loss Experiment ◽  
Oncogenic Function

Abstract Osteosarcoma (OS) is the most frequent primary bone malignancy and affects adolescents and young adults. Recently dysregulation of miRNAs has received more attention because of its extensive role in OS carcinogenesis. This research was designed to verify how microRNA-93 (miR-93) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2) be involved in OS development. At first, the levels of miR-93 and its predictive target gene TIMP2 were detected in OS and osteoblast cell lines, and 62 pairs OS and adjacent non-OS specimens by real-time PCR and western blot. Then, viability, invasion, and epithelial mesenchymal transition (EMT) of OS cell lines were examined when overexpressed or knocked down miR-93, or overexpressed TIMP2. Finally, the interaction between miR-93 and TIMP2 was evaluated using mutation, gain, and loss experiment. Our data indicated that miR-93 was increased while TIMP2 was decreased in both OS cell lines and tissues. MiR-93 high-expression and TIMP2 low-expression were related with poor overall survival and prognosis of OS patients. Overexpression or knockdown experiment indicated that miR-93 enhanced OS cell viability, invasion, and EMT expression. TIMP2 could inhibit OS cell viability, invasion, and EMT expression. Further, miR-93 directly targeted TIMP2 and negatively regulated TIMP2 level in OS cells. And up-regulation of TIMP2 reversed the effects of miR-93 in OS. Finally, miR-93 regulated the oncogenic functions in OS cells by regulating the expression of TIMP2. In conclusion, our study demonstrates that miR-93 may exert an oncogenic function while TIMP2 may act as a tumor suppressor on OS.

scholarly journals Tumor-Treating Fields Inhibit the Metastatic Potential of Osteosarcoma Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382094748
Author(s):  
Ju Yeon Oh ◽  
Yeon-Joo Lee ◽  
Eun Ho Kim
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Lung Metastases ◽  
Human Tumor ◽  
Metastatic Potential ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Tumor Cell Death ◽  
Mesenchymal Transition

The prognosis of metastatic osteosarcoma (OS) remains poor with a <20% survival rate, particularly in cases of distant (non-lung) metastases. Tumor-treating field (TTF) therapy is a novel electric field-based treatment that causes metaphase arrest and tumor cell death, with the advantage of reduced side effects compared to radiation and chemotherapy. TTF shows promise in glioblastoma and other solid tumors; however, few studies have examined its potential in the treatment of osteosarcoma. Therefore, we explored the mechanism of TTF-induced metastasis inhibition and cell death using in vitro models. TTF (1.5 V/cm, 150 kHz) was applied to U2OS and KHOS/NP OS cell lines. In addition, a 3-dimensional culture system was established using these OS cell lines. Cell migration and invasion (i.e., metastatic potential) were examined using a wound-healing scratch assay and transwell assay, respectively. Western blotting of metastasis- and angiogenesis-related proteins was performed. TTF suppressed the migration of and invasion by OS cells and inhibited the expression of epithelial markers, thereby preventing epithelial-mesenchymal transition (EMT), a hallmark of metastasis. Moreover, TTF prevented angiogenesis in human tumor endothelial cells and downregulated matrix metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF) expression. Therefore, TTF shows potential as an improved treatment for osteosarcoma, warranting further preclinical studies in animal models to support clinical trials.

scholarly journals Long Non-Coding RNA MALAT1 Decreases the Sensitivity of Resistant Glioblastoma Cell Lines to Temozolomide

2017 ◽  
Vol 42 (3) ◽  
pp. 1192-1201 ◽  
Author(s):  
Hongwei Li ◽  
Xiaoli Yuan ◽  
Dongming Yan ◽  
Dongpeng Li ◽  
Fangxia Guan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Biology ◽  
Glioblastoma Cell ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Glioblastoma Cell Lines

Background/Aim: Multidrug resistance (MDR) is largely responsible for the failure of chemotherapy. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript (MALAT1) has been reported to be closely related to tumor biology. In the present study, whether MALAT1 contributes to the resistance of glioblastoma cell lines to temozolomide (TMZ) was investigated. Methods: The glioblastoma cell lines U251 and U87 were exposed to increasing concentrations of TMZ to generate TMZ-resistant colonies (the U251/TMZ and U87/TMZ cell lines). The expression levels of MALAT1 and proteins related to epithelial-mesenchymal transition (EMT) were detected by real-time PCR and western blot, respectively. After the transfection of si-MALAT1 or pcDNA-MALAT1, cell viability, mRNA expression of MDR-associated proteins (MDR1, MRP5 and LRP1), and protein expression of EMT related proteins (ZEB1, Snail and SLUG) were evaluated. Results: The expression of MALAT1 was upregulated in the U251/TMZ and U87/TMZ cell lines compared to that in U251 and U87 cell lines, respectively. The treatment of si-MALAT1 decreased MDR1, MRP5, and LRP1 expression, enhanced cell sensitivity to TMZ, and downregulated ZEB1 protein expression, whereas pcDNA-MALAT1 had the opposite effects. However, the effects of si-MALAT1 on MDR -associated protein expression, cell viability, and EMT status were reversed by the transfection of pcDNA-ZEB1, and the effects of pcDNA-MALAT1 were reversed by the transfection of si-ZEB1. In vivo, MALAT1 overexpression enhanced tumors’ TMZ resistance and upregulated ZEB1 expression. Conclusion: MALAT1 decreased the sensitivity of resistant glioma cell lines to TMZ by regulating ZEB1.

scholarly journals Long non-coding RNA linc00645 promotes TGF-β-induced epithelial–mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chenlong Li ◽  
Hongshan Zheng ◽  
Weiliang Hou ◽  
Hongbo Bao ◽  
Jinsheng Xiong ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Vital Role ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition

Abstract Accumulating evidence indicates long noncoding RNAs (lncRNA) play a vital role in tumor progression. However, the role of linc00645-induced accelerated malignant behavior in glioblastoma (GBM) remains unknown. In the present study, linc00645 expression was significantly upregulated in GBM tissues and cell lines. High level of linc00645 was associated with poor overall survival in GBM patients. Knockdown of linc00645 suppressed the proliferation, stemness, migration, invasion, and reversed transforming growth factor (TGF)-β-induced motility of glioma cell lines. Furthermore, linc00645 directly interacted with miR-205-3p and upregulated of miR-205-3p impeded efficiently the increase of ZEB1 induced by linc00645 overexpression. Moreover, knockdown of linc00645 significantly suppressed the progression of glioma cells in vivo. miR-205-3p was a target of linc00645 and linc00645 modulates TGF-β-induced glioma cell migration and invasion via miR-205-3p. Taken together, our findings identified the linc00645/miR-205-3p/ZEB1 signaling axis as a key player in EMT of glioma cells triggered by TGF-β. These data elucidated that linc00645 plays an oncogenic role in glioma and it may serve as a prognostic biomarker and a potential therapeutic target for the treatment of glioma in humans.

scholarly journals Arctigenin Inhibits Cholangiocarcinoma Progression by Regulating Cell Migration and Cell Viability via the N-cadherin and Apoptosis Pathway

2021 ◽  
Author(s):  
Sutthiwan Janthamala ◽  
Apinya Jusakul ◽  
Sarinya Kongpetch ◽  
Phongsaran Kimawaha ◽  
Poramate Klanrit ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Viability ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Immunocytochemical Staining ◽  
Survival Times ◽  
Apoptosis Pathway ◽  
Mesenchymal Transition ◽  
The Impact

Abstract Northeast Thailand has the highest incidence of cholangiocarcinoma (CCA) in the world. The lack of promising diagnostic markers and appropriate therapeutic drugs are the main problem for metastatic stage CCA patients who have a poor prognosis. N-cadherin, a cell adhesion molecule, is usually upregulated in cancers and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT), one of the metastasis processes. Additionally, it has been shown that arctigenin, a seed extract from Arctium lappa, can inhibit cancer cell progression via suppression of N-cadherin pathway. In this study, we investigated the protein expression of N-cadherin and its correlation with clinicopathological data of CCA patients, as well as the impact of arctigenin on KKU-213A and KKU-100 CCA cell lines and its underlying mechanisms. Immunohistochemistry results demonstrated that high expression of N-cadherin was significantly associated with severe CCA stage (p=0.027), and shorter survival time (p=0.002) of CCA patients. The mean overall survival times between low and high expression of N-cadherin were 31.6 and 14.8 months, respectively. Wound healing assays showed that arctigenin significantly inhibited CCA cell migration by downregulating N-cadherin whereas upregulating E-cadherin expression. Immunocytochemical staining revealed that arctigenin suppressed the expression of N-cadherin in both CCA cell lines. Furthermore, flow cytometry and western blot analysis revealed that arctigenin significantly reduced CCA cell viability and induced apoptosis via the Bax/Bcl-2/Caspase-3 pathway. This research supports the use of N-cadherin as a prognostic marker for CCA and arctigenin as a potential alternative therapy for improving CCA treatment outcomes.

scholarly journals BAP-1 Inhibits Gastric Cancer Progression via PI3K/AKT Pathway by Suppressing FOXK1 Expression

2021 ◽  
Author(s):  
Chen Mi ◽  
Yan Zhao ◽  
Li Ren ◽  
Dan Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ags Cells ◽  
Mesenchymal Transition

Abstract BRCA1-Associated Protein-1 (BAP-1) gene functions as a vital mediator in tumor formation, progression, and metastasis. The involvement of BAP-1 in colon cancer has been widely reported, but the role of BAP-1 in gastric cancer (GC) is still unclear. In this study, we sought to investigate the contribution of BAP-1 in the pathogenesis of GC. qPCR and Western blot assay were used to detect the mRNA and protein expression of BAP-1 in GC cell lines. MTT and transwell assay were employed to determine the cell viability, migration, and invasion. Annexin V-PI double staining was used to evaluate cell apoptosis. We reported that BAP-1 was expressed at a low level in GC cell lines. Overexpression of BAP-1 inhibited cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) and promoted apoptosis in HGC-27 and AGS cells. BAP-1 inactivated the PI3K/AKT pathway by suppressing Forkhead-box K1 (FOXK1) expression. Moreover, overexpression of FOXK1 reversed the effect of BAP-1 on cell viability, apoptosis, migration, invasion, and EMT. Our data revealed that BAP-1 inhibits cell viability, migration, invasion, and EMT process and promoted apoptosis in HGC-27 and AGS cells through PI3K/AKT pathway via suppressing FOXK1 expression. Thus, BAP-1 can serve as a potential therapeutic target in GC treatment.

scholarly journals SMC1A facilitates gastric cancer cells proliferation, migration and invasion via promoting SNAI2 activated EMT

2021 ◽  
Author(s):  
Yaling Liu ◽  
Xianrui Fang ◽  
Qianqian Wang ◽  
Da Xiao ◽  
Zhenyu Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Cell ◽  
Vital Role ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Poor Overall Survival ◽  
Mesenchymal Transition

Background: structural maintenance of chromosomes protein 1A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participate in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC). Methods: RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT)were analyzed. Furthermore,the mechanism of SMC1A action was investigated. Results: SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS remarkably promoted cell proliferation, migration and invasion. While knockdown of SMC1A in HCG27 inhibited cell proliferation, migration and invasion of HGC27 cells. Moreover, it is observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAI2. Conclusion: our study revealed SMC1A facilitates gastric cancer cell proliferation, migration and invasion via promoting SNAI2 activated EMT, which indicated SMC1A may be a potential target for gastric cancer therapy.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Lisha Xie ◽  
Tao Jiang ◽  
Ailan Cheng ◽  
Ting Zhang ◽  
Pin Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

scholarly journals MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

2021 ◽  
Vol 20 ◽  
pp. 153303382198981
Author(s):  
Xin-bo Sun ◽  
Yong-wei Chen ◽  
Qi-sheng Yao ◽  
Xu-hua Chen ◽  
Min He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Proliferation And Apoptosis ◽  
High Incidence ◽  
Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

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