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 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 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 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 Long Non-Coding MALAT1 Functions as a Competing Endogenous RNA to Regulate Vimentin Expression by Sponging miR-30a-5p in Hepatocellular Carcinoma

2018 ◽  
Vol 50 (1) ◽  
pp. 108-120 ◽  
Author(s):  
Yujia Pan ◽  
Simeng Tong ◽  
Rongjun Cui ◽  
Jialin Fan ◽  
Chi Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Western Blotting ◽  
Normal Liver ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Vimentin Expression ◽  
Dual Luciferase Assay ◽  
Cell Migration And Invasion

Background/Aims: Hepatocellular carcinoma (HCC) has a high morbidity as well as mortality and is believed to be one of the most prevalent cancers worldwide. The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in numerous cancers, including HCC. This study aimed to explore the role of MALAT1 in HCC progression. Methods: The expression levels of MALAT1 and Vimentin in HCC tissues and relative pair-matched adjacent normal liver tissues were analyzed by RT-PCR, and immunohistochemistry. Using bioinformatics analysis and dual-luciferase assay, we examined the correlation between MALAT1 and miR-30a-5p. Dual-luciferase assay and western blotting suggested that Vimentin was a target of miR-30a-5p. A wound healing assay and transwell assays were employed to determine the effect of MALAT1 and miR-30a-5p on cell migration and invasion in HCC. Results: Our data demonstrated that the levels of MALAT1 and Vimentin were upregulated in HCC tissues and that miR-30a-5p was a direct target of MALAT1. Silenced MALAT1 and overexpressed miR-30a-5p each inhibited cell migration and invasion. Additionally, dual-luciferase assay and western blotting demonstrated that MALAT1 could competitively sponge miR-30a-5p and thereby regulate Vimentin. Conclusion: Our data suggest that MALAT1 acts as an oncogenic lncRNA that promotes HCC migration and invasion. Therefore, the MALAT1-miR-30a-5p-Vimentin axis is a potential therapeutic target and molecular biomarker in 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.

scholarly journals Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI

2019 ◽  
Vol 27 (9) ◽  
pp. 979-986 ◽  
Author(s):  
Jian-Wei Wang ◽  
Xiao-Feng Wu ◽  
Xiao-Juan Gu ◽  
Xing-Hua Jiang
Keyword(s):  
Cell Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Cancer Associated Fibroblasts ◽  
Osteosarcoma Cells ◽  
Mirna Microarray ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration

Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer exosomes to osteosarcoma cells, which promotes osteosarcoma cell migration and invasion. Using a miRNA microarray analysis, we identified 13 miRNAs that are significantly increased in exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding paracancer fibroblasts (PAFs). In vitro studies further validated that the levels of microRNA-1228 (miR-1228) were increased in CAFs, its secreted exosomes, and in recipient osteosarcoma cells, which can downregulate endogenous SCAI mRNA and protein level in osteosarcoma. Furthermore, our findings demonstrate that SCAI was downregulated in osteosarcoma tissues. Taken together, this study provides evidence that CAF exosomal miR-1228 is able to promote osteosarcoma invasion and migration by targeting SCAI, which may represent a critical therapeutic target for osteosarcoma treatment.

scholarly journals MiR-139-5p/SLC7A11 Inhibits the Proliferation and Migration of Pancreatic Carcinoma via PI3K/Akt Signaling Pathway

2019 ◽  
Author(s):  
Qiuliang Yan ◽  
Jianwei Wang ◽  
Yan Chen ◽  
Qinghuang Ye ◽  
Zhijiang Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Carcinoma ◽  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Inhibiting Effect ◽  
And Migration

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

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.

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