scholarly journals LINC00978 promotes the progression of hepatocellular carcinoma by regulating EZH2-mediated silencing of p21 and E-cadherin expression

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xueying Xu ◽  
Jianmei Gu ◽  
Xiaoge Ding ◽  
Guohong Ge ◽  
Xueyan Zang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Serum Levels ◽  
Migration And Invasion ◽  
Mouse Tumor ◽  
Clinical Value ◽  
Cycle Arrest ◽  
Tumor Tissues ◽  
E Cadherin

Abstract Long non-coding RNAs (lncRNAs) have been suggested as important regulators of cancer development and progression in hepatocellular carcinoma (HCC). Nevertheless, the clinical value and biological roles of LINC00978 in HCC remain unclear. In this study, we detected the expression of LINC00978 in tumor tissues and serum of HCC patients, examined the roles of LINC00978 in HCC progression and elucidated the underlying molecular mechanisms. We found that LINC00978 expression was upregulated in tumor tissues and serum of HCC patients. Higher serum levels of LINC00978 could distinguish HCC patients from hepatitis and liver cirrhosis patients and healthy controls. LINC00978 knockdown inhibited HCC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. Overexpression of LINC00978 led to the opposite effects. LINC00978 knockdown also inhibited HCC growth and metastasis in mouse tumor models. Mechanistically, LINC00978 bound to EZH2 and mediated its accumulation at the promoter region of p21 and E-cadherin genes, leading to the trimethylation of H27K3 and the inhibition of p21 and E-cadherin expression. Moreover, the simultaneous depletion of p21 and E-cadherin expression reversed the inhibitory effects of LINC00978 knockdown on HCC cell proliferation, migration, and invasion. Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing. LINC00978 may represent a novel biomarker for HCC diagnosis, prognosis, and therapy.

miR-3677-3p promotes hepatocellular carcinoma progression via inhibiting GSK3β

2020 ◽  
Vol 52 (12) ◽  
pp. 1404-1412
Author(s):  
Yanfei Li ◽  
Yajie Zhou ◽  
Linlin Ma ◽  
Dingsheng Liu ◽  
Zhensheng Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Untranslated Region ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3 ◽  
Diagnostic Biomarker ◽  
Tumor Tissues ◽  
Suppress Cell Proliferation ◽  
Hcc Cells

Abstract MicroRNAs play important roles in regulating hepatocellular carcinoma (HCC) formation, progression and metastasis. However, their functions and the underlying molecular mechanisms are still unclear. Here, we found that miR-3677-3p was highly expressed in primary tumor tissues of HCC patients. And its inhibition by using sponge in HCC cells could suppress cell proliferation significantly, but it has no effect on cell apoptosis. Through directly targeting to the 3′ untranslated region of glycogen synthase kinase 3-β (GSK3β), miR-3677-3p could inhibit GSK3β expression. Our study revealed that the miR-3677-3p/GSK3β axis may play a crucial role in HCC and miR-3677-3p may serve as a potential diagnostic biomarker or a therapeutic target for HCC.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

scholarly journals CircRNA LRIG3 knockdown inhibits hepatocellular carcinoma progression by regulating miR-223-3p and MAPK/ERK pathway

2021 ◽  
Author(s):  
Hui Sun ◽  
Junwei Zhai ◽  
Li Zhang ◽  
Yingnan Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Erk Pathway ◽  
Mitogen Activated Protein ◽  
Hcc Cells

IntroductionEmerging evidence suggests that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and molecular mechanisms of circRNA leucine-rich repeat immunoglobulin domain-containing protein 3 (circ_LRIG3) in hepatocellular carcinoma (HCC) has not been investigated.Material and methodsThe expression levels of circ_LRIG3, miR-223-3p, and mitogen-activated protein kinase kinase 6 (MAP2K6) were determined by qRT-PCR. Flow cytometry was applied to determine the cell cycle distribution and apoptosis. Cell proliferation, migration and invasion were assessed by MTT, colony formation, and transwell assays. Western blot assay was employed to measure the protein levels of the snail, E-cadherin, MAP2K6, mitogen-activated protein kinase (MAPK), phospho-MAPK (p-MAPK), extracellular signal-regulated kinases (ERKs), and phospho-ERKs (p- ERKs). The relationship between miR-223-3p and circ_LRIG3 or MAP2K6 was predicted by bioinformatics tools and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circ_LRIG3 in vivo.ResultsCirc_LRIG3 and MAP2K6 expression were enhanced while miR-223-3p abundance was reduced in HCC tissues and cells. Knockdown of circ_LRIG3 inhibited cell proliferation, metastasis, and increasing apoptosis. MiR-223-3p was a target of circ_LRIG3, and its downregulation reversed the inhibitory effect of circ_LRIG3 knockdown on the progression of HCC cells. Moreover, MAP2K6 could bind to miR-223-3p, and MAP2K6 upregulation also abolished the suppressive impact of circ_LRIG3 interference on progression of HCC cells. Additionally, the silence of circ_LRIG3 suppressed the activation of the MAPK/ERK pathway and tumor growth by upregulating miR-223-3p and downregulating MAP2K6.ConclusionsCirc_LRIG3 knockdown inhibited HCC progression through regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway.

Anlotinib Inhibits Cell Proliferation, Migration and Invasion via Suppression of c-met Pathway and Activation of ERK1/2 Pathway in H446 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiali Tang ◽  
Ying Zheng ◽  
Demin Jiao ◽  
Jun Chen ◽  
Xibang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
M Cell ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
And Migration

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

scholarly journals Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Conor C. Lynch ◽  
Tracy Vargo-Gogola ◽  
Lynn M. Matrisian ◽  
Barbara Fingleton
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Migration And Invasion ◽  
Cell Contact ◽  
E Cadherin ◽  
Cell Cell

Perturbations in cell-cell contact machinery occur frequently in epithelial cancers and result in increased cancer cell migration and invasion. Previously, we demonstrated that MMP-7, a protease implicated in mammary and intestinal tumor growth, can process the adherens junction component E-cadherin. This observation leads us to test whether MMP-7 processing of E-cadherin could directly impact cell proliferation in nontransformed epithelial cell lines (MDCK and C57MG). Our goal was to investigate the possibility that MMP-7 produced by cancer cells may have effects on adjacent normal epithelium. Here, we show that MMP-7 processing of E-cadherin mediates, (1) loss of cell-cell contact, (2) increased cell migration, (3) a loss of epithelial cell polarization and (4) increased cell proliferation via RhoA activation. These data demonstrate that MMP-7 promotes epithelial cell proliferation via the processing of E-cadherin and provide insights into the molecular mechanisms that govern epithelial cell growth.

scholarly journals miR-186 Suppresses the Progression of Cholangiocarcinoma Cells Through Inhibition of Twist1

2019 ◽  
Vol 27 (9) ◽  
pp. 1061-1068 ◽  
Author(s):  
Ming Zhang ◽  
Baochang Shi ◽  
Kai Zhang
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cycle Arrest

Deregulation of miR-186 and Twist1 has been identified to be involved in the progression of multiple cancers. However, the detailed molecular mechanisms underlying miR-186-involved cholangiocarcinoma (CCA) are still unknown. In this study, we found that miR-186 was downregulated in CCA tissues and cell lines, and negatively correlated with the expression of Twist1 protein. In vitro assays demonstrated that miR-186 mimics repressed cell proliferation, in vivo tumor formation, and caused cell cycle arrest. miR-186 mimics also inhibited the migration and invasion of CCLP1 and SG-231 cells. Mechanistically, the 3′-untranslated region (3′-UTR) of Twist1 mRNA is a direct target of miR-186. Further, miR-186 inhibited the expressions of Twist1, N-cadherin, vimentin, and matrix metallopeptidase 9 (MMP9) proteins, whereas it increased the expression of E-cadherin in CCLP1 and SG-231 cells. Silencing of Twist1 expression enhanced the inhibitory effects of miR-186 on the proliferation, migration, and invasion of CCLP1 and SG-231 cells. In conclusion, miR-186 inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) through targeting Twist1 in human CCA. Thus, miR-186/Twist1 axis may benefit the development of therapies for CCA.

scholarly journals LncRNA GSTM3TV2 Promotes Cell Proliferation and Invasion via miR-597/FOSL2 Axis in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yuting Hu ◽  
Wei Qiu ◽  
Zhijun Kong ◽  
Siyuan Wu ◽  
Yi Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Reporter Assays ◽  
Proliferation And Invasion

Mounting evidence has recently shown that role of long noncoding RNA is critical in many human cancers. lncRNA GSTM3TV2 was first proven to play a vital role in pancreatic cancer. However, the mechanism of lncRNA GSTM3TV2 in hepatocellular carcinoma (HCC) is still uncovered. Here, we object to distinguish the expression of lncRNA GSTM3TV2 and reveal its mechanistic relationship with HCC. We observed that the expression of lncRNA GSTM3TV2 and FOSL2 were upregulated in HCC. Knockdown of lncRNA GSTM3TV2 significantly inhibited cell proliferation. Meanwhile, the migration and invasion of HCC cells were greatly decreased by the downregulated lncRNA GSTM3TV2. The luciferase reporter assays showed that lncRNA GSTM3TV2 could be directly bound to miR-597, and the level of miR-597 was also decreased in the tumor tissues. lncRNA GSTM3TV2 could stabilize FOSL2 expression, resulting in the oncogenic properties of lncRNA GSTM3TV2 in HCC. Our study indicated the oncogenic activities of lncRNA GSTM3TV2 and emphasized the role of the miR-597/FOSL2 signaling pathway.

scholarly journals Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiejun Hu ◽  
Dong Cai ◽  
Zhibo Zhao ◽  
Guo-Chao Zhong ◽  
Jianping Gong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Advanced Tumor Stage ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Tumor Tissues ◽  
Nuclear Ribonucleoprotein

Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Furthermore, Cox proportional hazards regression models, the Kaplan–Meier method, and clinicopathologic features analysis showed that HNRNPC was not only an independent prognostic factor for both overall and disease-free survival in HCC but also a predictor of large tumor size and advanced tumor stage. Functional experiments revealed that silencing of HNRNPC not only led to arrest of more HCC cells at G0/G1 phase to inhibit their proliferation, but also suppressed EMT process to block their invasion, and migration in vitro; this was related to the Ras/MAPK signaling pathway. In addition, blocking of HCC cell proliferation regulated by HNRNPC silencing was observed in vivo. Finally, rescue tests showed that after recovery of Ras/MAPK signaling pathway activity by treatment with Ras agonists, the proliferation, migration, and invasion suppression of Huh-7 and Hep 3B cell lines caused by HNRNPC knockdown was partially reversed. Taken together, these results indicate that HNRNPC knockdown inhibits HCC cell proliferation, migration and invasion, in part via the Ras/MAPK signaling pathway. Thus, HNRNPC may have an important role in the progression of HCC and represents a promising biomarker for evaluation of prognosis and a potential therapeutic target in HCC patients.

scholarly journals Long non-coding RNA linc-ITGB1 promotes cell proliferation, migration, and invasion in human hepatoma carcinoma by up-regulating ROCK1

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Lei Huang ◽  
Xinyu Li ◽  
Weijie Gao
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Serum Levels ◽  
Migration And Invasion ◽  
Healthy Controls ◽  
Human Hepatoma ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Long Non Coding Rna ◽  
Hcc Cells

Background: Linc-ITGB1 is a newly identified long non-coding RNA (lncRNA) involved in the regulation of cell migration and invasion of gallbladder cancer cell lines, while its involvement in human hepatoma carcinoma (HCC) is unknown. Methods: In the present study, HCC patient tumor tissues, adjacent healthy tissues and whole blood were collected from both HCC patients and healthy controls. Expression of LINC-ITGB1 was examined by qRT-PCR. Diagnostic value of serum LINC-ITGB1 for HCC was evaluated by receiver operating characteristic (ROC) curve analysis. Correlation between the serum LINC-ITGB1 and basic clinical information of patients was analyzed by chi-square test. LINC-ITGB1 overexpression HCC cell lines were established and the effects on cell proliferation, migration, and invasion were explored by CCK-8 assay and Transwell assay. Effects of LINC-ITGB1 overexpression on Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) expression were investigated by Western blot. Results: We found that LINC-ITGB1 was up-regulated in tumor tissues than in adjacent healthy tissues. Serum levels of LINC-ITGB1 were higher in HCC patients than in healthy controls. Serum levels of LINC-ITGB1 were significantly correlated with tumor size and distant tumor metastasis. LINC-ITGB1 overexpression promoted the proliferation, migration, and invasion of HCC cells and the expression of ROCK1. ROCK1 inhibitor reduced the effects of LINC-ITGB1 overexpression on cell proliferation, migration, and invasion. Conclusion: We conclude that lncRNA LINC-ITGB1 can promote the proliferation, migration, and invasion of HCC cells by up-regulating ROCK1.

scholarly journals LncRNA CASC11 promotes cancer cell proliferation in hepatocellular carcinoma by inhibiting miRNA-188-5p

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Nan Cheng ◽  
Ju Wu ◽  
Min Yin ◽  
Jian Xu ◽  
Yadong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Cancer Cell Migration ◽  
Poor Survival ◽  
Tumor Tissues ◽  
Development Of Gastric Cancer

Abstract It is known that lncRNA CASC11 promotes the development of gastric cancer. Our study was carried out to investigate the possible involvement of ncRNA CASC11 in hepatocellular carcinoma (HCC). In the present study, we found that CASC11 was up-regulated, while miR-188-5p was down-regulated in tumor tissues of HCC patients. CASC11 and miR-188-5p were not affected by HBV and HCV infections. Follow-up study showed that high levels of CASC11 were significantly correlated with poor survival. Expression levels of CASC11 and miR-188-5p were inversely correlated in tumor tissues. CASC11 overexpression mediated the down-regulation of miR-188-5p, while miR-188-5p overexpression failed to affect CASC11 expression. CASC11 overexpression led to promoted, while miR-188-5p overexpression led to inhibited proliferation of cells of HCC cell lines. CASC11 overexpression showed no significant effects on cancer cell migration and invasion. In addition, miR-188-5p overexpression attenuated the enhancing effects of CASC11 overexpression on cancer cell proliferation. Therefore, LncRNA CASC11 promoted cancer cell proliferation in HCC possibly by inhibiting miR-188-5p.

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