scholarly journals lncRNA DLGAP1-AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR-154-5p Methylation

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kai Chen ◽  
Zhuqing Zhang ◽  
Aijun Yu ◽  
Jian Li ◽  
Jinlong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Migration And Invasion ◽  
Altered Expression ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Specific Pcr ◽  
And Migration ◽  
Hcc Cells

Objective. DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. Our preliminary microarray analysis revealed the altered expression of DLGAP1-AS2 in hepatocellular carcinoma (HCC), but the role of DLGAP1-AS2 in HCC remains unknown. Method. Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and nontumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 knockdown and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay. Results. DLGAP1-AS2 was upregulated in HCC and predicted poor survival. miR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 knockdown resulted in the upregulation of miR-154-5p expression and decreased methylation of miR-154-5p gene. Transwell assay showed that DLGAP1-AS2 knockdown and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 knockdown and miR-154-5p overexpression showed stronger effects. Conclusion. DLGAP1-AS2 knockdown may inhibit HCC cell migration and invasion by regulating miR-154-5p methylation.

scholarly journals Inhibiting roles of FOXA2 in hepatocellular carcinoma cell migration and invasion by transcriptionally suppressing microRNA-103a-3p and activating the GREM2/LATS2 axis

2020 ◽  
Author(s):  
Guangzhen Ma ◽  
Jirong Chen ◽  
Tiantian Wei ◽  
Jia Wang ◽  
Wenshan Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Altered Expression ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Forkhead Box ◽  
And Migration

Abstract Background Forkhead box A2 (FOXA2) is a transcriptional activator for liver-specific genes. Hepatocellular carcinoma (HCC) is a prevalent fetal malignancy across the globe. This work focused on the role of FOXA2 in HCC cell migration and invasion and the involving molecules. Methods FOXA2 expression in HCC tissues and cells was determined using RT-qPCR. Altered expression of FOXA2 was introduced to identify its role in HCC cell migration and invasion using Transwell assays. The potential target microRNA (miRNA) of FOXA2 was predicted via online prediction and validated through a ChIP assay, and the mRNA target of miRNA-103a-3p was predicted and confirmed through a luciferase assay. The roles of miR-103a-3p and GREM2 in HCC cell invasion and migration were determined, and the downstream molecules mediated by GREM2 were analyzed. Results FOXA2 and GREM2 were poorly expressed while miR-103a-3p was abundant in HCC tissues and cells. Overexpression of FOXA2 or GREM2 suppressed migration and invasion of HepG2 and SK-HEP-1 cells, while up-regulation of miR-103a-3p led to reverse trends. FOXA2 transcriptionally suppressed miR-103a-3p to increase GREM2 expression, and silencing of GREM2 partially blocked the inhibitory effects of FOXA2 on cell migration and invasion. GREM2 increased LATS2 activity and YAP phosphorylation and degradation. Conclusion This study evidenced that FOXA2 inhibits migration and invasion potentials of HCC cell lines through suppressing miR-103a-3p transcription. The following upregulation of GREM2 plays key roles in migration inhibition by promoting LATS2 activity and YAP phosphorylation. This study may offer new insights into HCC treatment.

scholarly journals LncRNA DLGAP1-AS2 SiRNA Silencing Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Up-regulating MiR-154-5p Through Methylation

2020 ◽  
Author(s):  
Kai Chen ◽  
Zhuqing Zhang ◽  
Aijun Yu ◽  
Jian Li ◽  
Jinlong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Specific Pcr ◽  
Tumor Tissues ◽  
Sirna Silencing ◽  
And Migration ◽  
Hcc Cells

Abstract Background:DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. This study was performed to explore the role of DLGAP1-AS2 in hepatocellular carcinoma (HCC). Methods:Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and non-tumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay.Results: DLGAP1-AS2 was upregulated in HCC and predicted poor survival. MiR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 siRNA silencing resulted in the upregulation of miR-154-5p and decreased methylation of miR-154-5p gene. Transwell assay showed that, DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 siRNA silencing and miR-154-5p overexpression showed stronger effects.Conclusion: DLGAP1-AS2 siRNA silencing may inhibit HCC cell migration and invasion by up-regulating miR-154-5p through methylation.

scholarly journals LncRNA SAMMSON negatively regulates miR-9-3p in hepatocellular carcinoma cells and has prognostic values

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Shouzhang Yang ◽  
Huajie Cai ◽  
Bingren Hu ◽  
Jinfu Tu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Cancer Cell ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Expression Levels ◽  
Cell Migration And Invasion ◽  
Hcc Cells

Abstract In the present study, we investigated the role of lncRNA SAMMSON in hepatocellular carcinoma (HCC). We found that SAMMSON was up-regulated in HCC tissues, and patients with high levels of SAMMSON in HCC tissues had significantly lower overall rate within 5 years after admission. miR-9-3p was down-regulated in HCC tissues and inversely correlated with SAMMSON. SAMMSON expression was not significantly affected by HBV and HCV infections in HCC patients. In HCC cells, SAMMSON overexpression resulted in down-regulated miR-9-3p expression, while miR-9-3p overexpression caused no significant changes in expression levels of SAMMSON. SAMMSON overexpression led to increased, while miR-9-3p overexpression resulted in decreased migration and invasion rates of HCC cells. Therefore, SAMMSON negatively regulated miR-9-3p in HCC cells to promote cancer cell migration and invasion.

scholarly journals Down-regulation of microRNA-34a-5p promotes trophoblast cell migration and invasion via targetting Smad4

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Fang Xue ◽  
Jing Yang ◽  
Qirong Li ◽  
Haibin Zhou
Keyword(s):  
Cell Migration ◽  
Expression Profiles ◽  
Trophoblast Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Luciferase Activity Assay ◽  
Cell Invasiveness ◽  
And Migration ◽  
Mirnas Expression

Abstract Trophoblastic dysfunction, such as insufficient migration and invasion, is well-known to be correlated with preeclampsia (PE). Recently, microRNAs (miRNAs) have been implicated in diverse biological processes and human diseases, including PE. However, the expression and functions of miRNAs in the progression of PE, especially in the regulation of trophoblast cell migration and invasion remain largely unclear. Here, we compared the miRNAs expression profiles of PE patients with healthy controls using microarray assay and chose a significant increased miRNA-miR-34a-5p for further investigation. Overexpression of miR-34a-5p dramatically reduced migration and invasion in trophoblast HTR-8/SVneo cells, whereas enhanced by its inhibitor. Luciferase activity assay showed that miR-34a-5p directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis. We also found that Smad4 was down-regulated in PE patients, and an inverse relationship between Smad4 and miR-34a-5p expression levels was observed in placental tissues from PE patients. Further study showed that knockdown of Smad4 effectively attenuated the promoting effects of miR-34a-5p inhibition on the migration and invasion of HTR-8/SVneo cells. Taken together, these findings suggest that inhibition of miR-34a-5p improves invasion and migration of trophoblast cells by directly targetting Smad4, which indicated the potential of miR-34a-5p as a therapeutic target against PE.

scholarly journals MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R

2018 ◽  
Vol 26 (9) ◽  
pp. 1391-1399 ◽  
Author(s):  
Zeng Cheng Zou ◽  
Min Dai ◽  
Zeng Yin Huang ◽  
Yi Lu ◽  
He Ping Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Cell Growth ◽  
Mouse Model ◽  
Migration And Invasion ◽  
Tumor Growth And Metastasis ◽  
Underlying Mechanisms ◽  
Hcc Cells

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues. Exogenous overexpression of miR-139-3p inhibited the migration and invasion of HCC cells, whereas downregulation of miR-139-3p was able to induce HCC HepG2 and SNU-449 cell migration and invasion. In addition, miR-139-3p inhibited HCC growth and lung metastasis in an in vivo mouse model, which is mainly regulated by annexin A2 receptor (ANXA2R). Finally, we identified that the expression of miR-139-3p was inversely correlated with ANXA2R expression in human HCC tissue. All these results demonstrated that miR-139-3p inhibited the metastasis process in HCC by downregulating ANXA2R expression.

scholarly journals Total flavonoids of Radix Tetrastigma suppress inflammation-related hepatocellular carcinoma cell metastasis

2021 ◽  
Author(s):  
Zhendong Liu ◽  
Fangmi Ding ◽  
Xingyong Shen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Total Flavonoids ◽  
Cell Migration And Invasion ◽  
Proinflammatory Mediators ◽  
Cox 2 ◽  
Hcc Cells

AbstractThis study aimed to investigate the effects of the total flavonoids of Radix Tetrastigma (RTF) on inflammation-related hepatocellular carcinoma (HCC) development. Extracted RTF was diluted to different concentrations for subsequent experiments. HCC cells were cotreated with lipopolysaccharide (LPS) and RTF to investigate the effects of RTF on LPS-stimulated HCC cells. A CCK-8 kit was used to measure cell proliferation. Apoptosis was detected with a flow cytometer. Cell migration and invasion were quantified by wound healing and Transwell assays, respectively. The expression of TLR4 and COX-2 and activation of the NF-κB pathway were determined by Western blotting. Treatment with LPS significantly enhanced cell proliferation and decreased the apoptosis rate, while cell migration and invasion were notably upregulated. RTF suppressed the proliferation and invasion induced by LPS stimulation and promoted HCC cell apoptosis. The protein levels of Bax and cleaved caspase-3 were decreased and that of Bcl-2 was increased by LPS in HCC cells, which could be rescued by RTF. RTF significantly inhibited the LPS-induced expression of the proinflammatory mediators IL-6 and IL-8 in HCC cells. Mechanistically, with RTF treatment, the upregulated expression of TLR4 and COX-2 induced by LPS was obviously downregulated. Furthermore, the phosphorylation of NF-κB/p65 was significantly decreased in LPS-stimulated cells after supplementation with RTF. Our study suggests that RTF exerts a significant inhibitory effect on the LPS-induced enhancement of the malignant behaviors of HCC cells via inactivation of TLR4/NF-κB signaling. RTF may be a promising chemotherapeutic agent to limit HCC development and inflammation-mediated metastasis.

scholarly journals ASIC1a Stimulates the Resistance of Human Hepatocellular Carcinoma by Promoting Epithelial-mesenchymal Transition via the AKT/GSK3β/Snail Signaling Pathway

2021 ◽  
Author(s):  
Yinci Zhang ◽  
Niandie Cao ◽  
Jiafeng Gao ◽  
Jiaojiao Liang ◽  
Yong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Cell Migration ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Gsk 3Β ◽  
Hcc Cells

Abstract Background: The main obstacle to the cure of hepatocellular carcinoma (HCC) is multidrug resistance. Acid sensing ion channel 1a (ASIC1a) acts as a critical roles in all stages of cancer progression, especially invasion and metastasis as well as in resistance to therapy. Epithelial to mesenchymal transition (EMT) is a phenomenon in which epithelial cells transform into mesenchymal cells after being stimulated by extracellular factors and is closely related to tumor infiltration and resistance. Methods: Western blotting assay, Immunofluorescence (IF) staining, Immunohistochemistry (IHC) staining, MTT and colony formation assay and scratch healing assay were used to detect the level of ASIC1a and the cell proliferation, migration and invasion capabilities in this research.Results: In this research, we found that the protein of ASIC1a is overexpressed in HCC cancer tissues. In addition, we identified that the levels of ASIC1a are highly expressed in resistant HCC cells. Compared with the parental cells, EMT occurred more frequently in drug-resistant cells. Functional studies demonstrated that inactivation of ASIC1a restrained cell migration and invasion and enhanced the chemosensitivity of cells through EMT. In HCC cells, the overexpression of ASIC1a stimulates the up-regulation of EMT characterization molecular level and proliferation, migration and invasion capabilities and further induces drug resistance, while knocking down ASIC1a with short hairpin RNA (shRNA) has the opposite effect. Further investigations found that ASIC1a increased cell migration and invasion through EMT by regulating α and β-catenin, vimentin and fibronectin expression via AKT/GSK-3β/Snail pathway. Conclusions: Our study demonstrated that ASIC1a acts an important assignment in drug resistance of HCC through EMT via AKT/GSK-3β/Snail pathway, thereby lending a latent therapeutic objective and new ideas regarding to HCC.

scholarly journals MiR-3150b inhibits hepatocellular carcinoma cell proliferation, migration and invasion by targeting GOLPH3

2019 ◽  
Vol 68 (3) ◽  
pp. 770-775
Author(s):  
Yi Zhang ◽  
Jianjun Wang ◽  
Hongling Su
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Carcinoma Cell ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Hepatocellular Carcinoma Cell ◽  
And Migration ◽  
Hcc Cells

BackgroundIn this study, we aimed to explore the potential involvement of miR-3150b in hepatocellular carcinoma (HCC) carcinogenesis.MethodsThe expression of miR-3150b and Golgi phosphoprotein 3 (GOLPH3) was determined in HCC cell lines. Cell proliferation, migration and invasion were estimated by Cell Counting Kit-8, wound healing and Transwell assays. The association between miR-3150b and GOLPH3 was verified by luciferase assay.ResultsMiR-3150b was downregulated, while GOLPH3 was remarkably upregulated in HCC cells. Furthermore, miR-3150b inhibited HCC cell proliferation, migration and invasion. MiR-3150b directly targeted and negatively regulated GOLPH3.ConclusionMiR-3150b suppressed HCC cell proliferation, invasion and migration by targeting GOLPH3.

Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells

2021 ◽  
pp. 153537022110356
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Rongxue Peng ◽  
Jinming Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Hepatocellular Carcinoma Cells ◽  
Virus Like Particles ◽  
Invasion And Migration ◽  
Mrna Targets ◽  
And Migration ◽  
Microrna Dysregulation ◽  
Hcc Cells

MicroRNAs are related to the development of hepatocellular carcinoma and can serve as potential therapeutic targets. Therapeutic strategies increasing tumor-suppressive microRNAs and reducing oncogenic microRNAs have been developed. Herein, the effects of simultaneously altering two microRNAs using MS2 virus-like particles were studied. The sequences of microRNA-21-sponge and pre-microRNA-122 were connected and cloned into a virus-like particle expression vector. Virus-like particles containing microRNA-21-sponge and pre-microRNA-122 sequences were prepared and crosslinked with a cell-specific peptide targeting hepatocellular carcinoma cells. Delivery effects were studied using RT-qPCR and functional assays to investigate the level of target mRNAs, cell toxicity, and the effects of proliferation, invasion, and migration. Virus-like particles delivered miR-21-sponge into cells, with the Ct value reaching 10 at most. The linked pre-miR-122 was processed into mature miR-122. The mRNA targets of miR-21 were derepressed as predicted and upregulated 1.2–2.8-fold, and the expression of proteins was elevated correspondingly. Proliferation, migration, and invasion of HCC cells were inhibited by miR-21-sponge. Simultaneous delivery of miR-21-sponge and miR-122 further decreased proliferation, migration, and invasion by up to 34%, 63%, and 65%, respectively. And the combination promoted the apoptosis of HCC cells. In conclusion, delivering miR-21-sponge and miR-122 using virus-like particles modified by cell-specific peptides is an effective and convenient strategy to correct microRNA dysregulation in hepatocellular carcinoma cells and is a promising therapeutic strategy for hepatocellular carcinoma.

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