scholarly journals Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Fan He ◽  
Guoming Ding ◽  
Wu Jiang ◽  
Xiaoliang Fan ◽  
Liulong Zhu
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Mononuclear Cells ◽  
Epithelial Mesenchymal Transition ◽  
Pdz Domain ◽  
Inhibitory Effect ◽  
Tumor Associated Macrophages ◽  
Peripheral Blood Mononuclear ◽  
Mesenchymal Transition ◽  
Upstream Regulator

AbstractTumor-associated macrophages (TAMs) are known to participate in osteosarcoma (OS) progression. As demonstrated in our previous research, miR-363 played a tumor inhibitory effect in OS cells via lowering the PDZ domain containing 2 (PDZD2) expression. The regulatory roles of TAMs on miR-363/PDZD2 and the internal mechanism relating to long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) are examined in this study. TAM-like macrophages were formed by inducing CD14+ peripheral blood mononuclear cells (PBMCs). The TAMs migration was detected after MG-63 cells transfected with miR-363 mimics or inhibitors. We then analyzed the regulatory activity of PURPL on miR-363 expression. We also tested the influences of PURPL overexpression/knockdown on MG-63 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as TAMs migration. Silence in PDZD2 expression was used to confirm the effects of PURPL on MG-63 cells. We successfully induced TAM-like macrophages. MG-63 cells transfecting miR-363 mimics suppressed TAMs migration while transfecting a converse effect was seen in miR-363 inhibitor. TAMs raised PURPL expression in MG-63 cells, which was an upstream regulator of miR-363. Along with TAMs migration, PURPL overexpression promoted MG-63 cell proliferation, migration, invasion, and EMT. An opposite influence was seen due to the PURPL knockdown. The silence of PDZD2 weakened the influences of PURPL overexpression on MG-63 cells and TAMs migration. On modulating the PURPL/miR-363/PDZD2 axis, TAMs-promoted OS development might be achieved.

scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

Circulating tumor cells (CTCs) and epithelial mesenchymal transition (EMT) in primary breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22023-e22023 ◽  
Author(s):  
Marian Karaba ◽  
Michal Mego ◽  
Gabriel Minarik ◽  
Juraj Benca ◽  
Tatiana Sedlackova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Mononuclear Cells ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Peripheral Blood Mononuclear ◽  
Mesenchymal Transition ◽  
Cancer Pathogenesis ◽  
Tumor Dissemination ◽  
Gene Transcripts

e22023 Background: CTCs are prognostic in breast cancer (BC) patients and represent a heterogeneous population of cells with different phenotypes and biological value. EMT gives rise to cells with stem cell-like properties with increased chemotherapy resistance and may be responsible for under detection of CTCs by currently approved assays. The aim of this study was to characterize CTCs based on the expression of epithelial and mesenchymal markers in non-metastatic BC patients. Methods: This prospective ongoing study included 124 patients (pts) with non-metastatic BC enrolled from March 2012 to December 2012. CTCs were detected before surgery (124 pts), before 1st cycle (28 pts) and before 2nd cycle (23 pts) of adjuvant therapy. Isolated peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep kit negative selection with anti-CD45 antibody. RNA extracted from CD45-depleted (CD45-) PBMC was interrogated for expression of EMT-inducing transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Expressions of gene transcripts in CD45- PBMC of patients were compared to those of CD45- PBMC of 60 healthy donors. Results: CTCs were detected in 26.6% pts before surgery, in 21.4% pts before 1st cycle and in 43.5% of pts before 2nd cycle of adjuvant therapy. Before surgery, CTCs exhibiting only epithelial makers were present in 12.9% pts, whereas CTCs with only EMT markers were observed in 12.1% of pts and CTCs coepressing both markers were detected in 1.6% pts. There was a trend for higher CTC positivity in high grade, triple negative tumors and in the presence of lymphovascular invasion. We detected CTCs with only an EMT phenotype more often in pts with N+ than in N0 disease (20.4% vs. 10.2%; p = 0.03) and in pts after 1stcycle of adjuvant chemotherapy compared to before surgery (30.4% vs. 12.1%; p = 0.03). There was no association between epithelial CTCs and analyzed clinico-pathological variables. Conclusions: Our data suggest that CTCs with EMT phenotype are involved in tumor dissemination and treatment resistance, and support the role of EMT in cancer pathogenesis. Moreover, these results underlay the concept of CTCs heterogeneity.

scholarly journals SIRT3 Inhibits Cholangiocarcinoma Cell Proliferation by Targeting HIF1α to regulate the EMT Signaling Pathway

2021 ◽  
Author(s):  
Yihang Zhao ◽  
Yaxian Kuai ◽  
Jianhua Xu ◽  
Yufang Cui ◽  
Juan Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Protein Acetylation ◽  
Mesenchymal Transition ◽  
Cholangiocarcinoma Cell ◽  
Poor Outcomes ◽  
Medical University ◽  
The Relationship

Abstract BackgroundCholangiocarcinoma (CCA), is a rare biliary adenocarcinoma associated with poor outcomes. Deacetylase Sirtuin‐3 (SIRT3), a histone deacetylase (HDAC), has been considered to be associated with various cancers and can be a potential new target for CCA.We intended to identify the target of SIRT3 and explore the mechanism of SIRT3 in CCA.MethodsThe expression levels of SIRT3 and hypoxia‐inducible factor‐1α (HIF1α) in CCA tissues and cell lines were examined by RT-qPCR. CCK-8 and EdU methods were used to detect cell proliferation in CCA. To assess the levels of proteins related to cell proliferation and epithelial-mesenchymal transition (EMT) process, western blot analysis was conducted. Co-Immunoprecipitation and deacetylation assays were used to explore HIF1α protein acetylation, stability and the relationship between SIRT3 and HIF1α in CCA cells.ResultsSIRT3 showed low expression in CCA tissues and cells. SIRT3 overexpression inhibited cell proliferation and EMT process. Moreover, the interaction between SIRT3 and HIF1α was confirmed and HIF1α expression was negatively regulated by SIRT3. Furthermore, we also found that HIF1α was more easily degraded and showed a reduction in stability through deacetylation via SIRT3 knockdown. In rescue assays, HIF1α also reversed the inhibitory effect of SIRT3 on cell proliferation and the EMT process. ConclusionsSIRT3 suppressed cell proliferation and the EMT process in CCA by targeting HIF1α.Trial registrationSamples were obtained only after the patient has given informed consent according to the established plan approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University.

Downregulation of long noncoding RNA T1NCR inhibits cell proliferation, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma

2021 ◽  
Vol 7 (6) ◽  
pp. 6499-6510
Author(s):  
Hongjuan Li ◽  
Yaqin Chen ◽  
Chunyan Wu ◽  
Haiyan Zhao ◽  
Xuesong Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Proliferation Ability ◽  
Non Coding Rnas

Accumulating reports have identified that long non-coding RNAs (IncRNAs) function as key regulators of tumor initiation and progression. The aim of the current study was to determine the clinical significance and functional role of TINCR in hepatocellular carcinoma (HCC). In the present study, the level of IncRNA TINCR expression was significantly upregulated in HCC tissues compared to adjacent normal tissues. Higher levels of IncRNA TINCR expression were significantly correlated with tumor size and vascular invasion of HCC patients. LncRNA TINCR knockdown inhibited cell proliferation ability, increased the proportion of G1 phase cells, reduced the proportion of S phase cells, and suppressed cell invasion of HCC in vitro. Additionally, IncRNA TINCR knockdown inhibited the HCC cell epithelial-mesenchymal transition (EMT) phenomenon by upregulating E-cadherin and reducing N-cadherin expression. We demonstrated that knockdown of IncRNA reduced tumor growth in vivo. Thus, these results indicated that IncRNA TINCR exhibits a tumor oncogenic role in HCC and inhibition of IncRNA TINCR might serve as a therapeutic target for HCC.

scholarly journals Chemerin Isoform-Specific Effects on Hepatocyte Migration and Immune Cell Inflammation

2020 ◽  
Vol 21 (19) ◽  
pp. 7205 ◽  
Author(s):  
Susanne Feder ◽  
Astrid Bruckmann ◽  
Nichole McMullen ◽  
Christopher J. Sinal ◽  
Christa Buechler
Keyword(s):  
Cell Culture ◽  
Culture Medium ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Protective Effects ◽  
Cell Culture Medium ◽  
Peripheral Blood Mononuclear ◽  
Mesenchymal Transition ◽  
Huh7 Cells

Murine chemerin is C-terminally processed to the bioactive isoforms, muChem-156 and muChem-155, among which the longer variant protects from hepatocellular carcinoma (HCC). However, the role of muChem-155 is mostly unknown. Here, we aimed to compare the effects of these isoforms on the proliferation, migration and the secretome of the human hepatocyte cell lines HepG2 and Huh7 and the murine Hepa1-6 cell line. Therefore, huChem-157 and -156 were overexpressed in the human cells, and the respective murine variants, muChem-156 and -155, in the murine hepatocytes. Both chemerin isoforms produced by HepG2 and Hepa1-6 cells activated the chemerin receptors chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor 1 (GPR1). HuChem-157 was the active isoform in the Huh7 cell culture medium. The potencies of muChem-155 and muChem-156 to activate human GPR1 and mouse CMKLR1 were equivalent. Human CMKLR1 was most responsive to muChem-156. Chemerin variants showed no effect on cell viability and proliferation. Activation of the mitogen-activated protein kinases Erk1/2 and p38, and protein levels of the epithelial–mesenchymal transition marker, E-cadherin, were not regulated by the chemerin variants. Migration was reduced in HepG2 and Hepa1-6 cells by the longer isoform. Protective effects of chemerin in HCC include the modulation of cytokines but huChem-156 and huChem-157 overexpression did not change IL-8, CCL20 or osteopontin in the hepatocytes. The conditioned medium of the transfected hepatocytes failed to alter these soluble factors in the cell culture medium of peripheral blood mononuclear cells (PBMCs). Interestingly, the cell culture medium of Huh7 cells producing the inactive variant huChem-155 reduced CCL2 and IL-8 in PBMCs. To sum up, huChem-157 and muChem-156 inhibited hepatocyte migration and may protect from HCC metastasis. HuChem-155 was the only human isoform exerting anti-inflammatory effects on immune cells.

Long noncoding RNA MAGI2-AS3 inhibits bladder cancer progression through MAGI2/PTEN/epithelial-mesenchymal transition (EMT) axis

2020 ◽  
pp. 1-11
Author(s):  
Daqing Shen ◽  
Jing Xu ◽  
Xiande Cao ◽  
Xianxiang Cao ◽  
Hailin Tan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Pdz Domain ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Pten Gene ◽  
Mesenchymal Transition

BACKGROUND: Long noncoding RNA (lncRNA) are critical regulators of tumor progression. OBJECTIVE: To determine how the lncRNA membrane associated guanylate kinase, WW and PDZ domain-containing 2 (MAG12) antisense RNA 3 (MAGI2-AS3) and the phosphatase and tensin homolog (PTEN) gene function in regulating bladder cancer (Bca) progression. METHODS: Total RNA from 80 and 30 paired resected Bca and para-cancerous tissues from patients with confirmed Bca was sequentially extracted, quantified, purified, and reverse transcribed using RT-PCR. A library was constructed and sequenced. Four Bca cell lines and a normal urothelial cell line were transfected with lentiviral plasmids, and cell migration and invasion were assayed in vitro. An orthotopic mouse model of Bca was created for in vivo studies. RESULTS: MAGI2-AS3 expression was significantly downregulated in Bca, compared with normal tissues, and negatively associated with tumor stage and a poor prognosis. MAGI2-AS3 and its sense RNA MAGI2 showed significant and positive correlation. The expression of MAGI2 and its downstream gene, PTEN, increased in Bca cells overexpressing MAGI2-AS3, and interference by MAGI2 expression reversed the migration and invasion inhibited by MAGI2-AS3 overexpression. CONCLUSION: MAGI2-AS3 overexpression inhibited Bca cell progression by regulating the MAGI2/PTEN/epithelial-mesenchymal transition, offering novel insights into the mechanism of Bca progression.

scholarly journals LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Wenhu Chen ◽  
Lifang Wang ◽  
Xiaoyan Li ◽  
Changan Zhao ◽  
Liang Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Software Analysis

AbstractSmall nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous “sponge” competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

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