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.

scholarly journals MicroRNA-214-5p Inhibits the Invasion and Migration of Hepatocellular Carcinoma Cells by Targeting Wiskott-Aldrich Syndrome Like

2018 ◽  
Vol 46 (2) ◽  
pp. 757-764 ◽  
Author(s):  
Hongdan Li ◽  
Haoqi Wang ◽  
Zhen Ren
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Hepatocellular Carcinoma Cells ◽  
Invasion And Migration ◽  
Wiskott Aldrich Syndrome ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
And Migration

Background/Aims: This study aims to explore the effects of microRNA-214-5p (miR-214-5p) on the invasion and migration of Hepatocellular Carcinoma cells (HCC). Methods: Hepatocellular Carcinoma tissues and adjacent normal tissues from 44 hepatocellular carcinoma patients were prepared for this study. The HepG2 and BEL-7402 cells were transfected with miR-214-5p mimic and inhibitor. qRT-PCR was performed to detect the expressions of miR-214-5p. Transwell assays were used to detect the invasion and migration assays in HepG2 and BEL-7402 cells. A dual-luciferase reporter assay was conducted to examine the effect of miR-214-5p on Wiskott-Aldrich Syndrome Like (WASL/ N-WASP). Western blot and qRT-PCR were used to measure the expressions of the E-cadherin, N-cadherin and Vimentin proteins. Transwell chamber assays were performed to detect cell invasion and migration. Results: Compared with normal tissues, HCC tissues demonstrated significantly lower expression of miR-214-5p. Overexpression of miR-214-5p significantly inhibited the migration and invasion of HCC cells and inhibition of miR-214-5p promoted the migration and invasion. Additionally, miR-214-5p suppressed the epithelial-mesenchymal transition (EMT). Further study showed WASL was a putative target gene of miR-214-5p. Up-regulating the expression of WASL could reverse the inhibition effect of miR-214-5p on invasion and migration. Conclusion: Our data suggested that miR-214-5p inhibited the invasion and migration of HepG2 and BEL-7402 by targeting WASL in Hepatocellular carcinoma.

scholarly journals A long non-coding RNA lncRNA-PE promotes invasion and epithelial–mesenchymal transition in hepatocellular carcinoma through the miR-200a/b-ZEB1 pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770575 ◽  
Author(s):  
Yuan Shen ◽  
Shanshan Liu ◽  
Hanyu Yuan ◽  
Xiaomin Ying ◽  
Hanjiang Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
Hepatocellular Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Long non-coding RNAs have been revealed to play important roles in the progression of hepatocellular carcinoma. However, the detailed mechanisms underlying their activities are not fully understood. Using microarray technology, a number of long non-coding RNAs were previously identified to be aberrantly expressed in hepatocellular carcinoma. In this study, one of these long non-coding RNAs, designated lncRNA-PE (lncRNA promotes epithelial–mesenchymal transition), was further explored to study its expression profile and function. A cohort of human hepatocellular carcinoma tissue samples combined with benign controls and established human hepatocellular carcinoma cell lines were examined for the expression of lncRNA-PE. The biological functions of lncRNA-PE were examined by wound-healing and Transwell assays, which revealed that lncRNA-PE promotes cell invasion and migration. By detecting the level of epithelial–mesenchymal transition markers, lncRNA-PE was revealed to promote epithelial–mesenchymal transition in hepatocellular carcinoma cells. Further study suggested that lncRNA-PE downregulated miR-200a/b by repressing the primary transcript expression, enhanced ZEB1 expression, and promoted epithelial–mesenchymal transition of hepatocellular carcinoma cells. All these data imply that lncRNA-PE might play an important role in hepatocellular carcinoma development via the miR-200a/b-ZEB1 pathway.

scholarly journals miR-100 Suppresses the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma Cells via Targeting CXCR7

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yiman Ge ◽  
Jia Shu ◽  
Gang Shi ◽  
Fuguo Yan ◽  
Yejing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Antitumor Effects ◽  
Hepatocellular Carcinoma Cells ◽  
Invasion And Migration ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Endothelial Growth Factor

This study is to elucidate the functions of miR-100 in hepatocellular carcinoma progression and to explore the underlying mechanisms. Expression levels of miR-100 in normal-cancer hepatocellular carcinoma tissues were measured using quantitative real-time PCR (qRT-PCR). The invasive and proliferative abilities of hepatocellular carcinoma cell lines transfected with mimic-NC or mimic-miR-100 were measured using transwell, CCK-8, and colony formation assays. The binding sites between CXCR7 and miR-100 were determined using luciferase reporter assays. The correlation of CXCR7 and miR-100 in hepatocellular carcinoma progression was further confirmed by cotransfection assays. Our results showed that miR-100 was significantly lower expressed in hepatocellular carcinoma tissues and negatively associated with CXCR7 expression. Cell functional assays’ results found that upregulation of miR-100 inhibited the proliferative, invasive, and migrative abilities in hepatocellular carcinoma cells. Luciferase reporter assay suggested that CXCR7 mRNA and miR-100 bound one another. Increasing CXCR7 expression reversed the inhibitive effects of upregulated miR-100 in hepatocellular carcinoma cells. Further study showed that miR-100/CXCR7 played a role in hepatocellular carcinoma progression by regulating metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF). Conclusively, miR-100 exerts antitumor effects on hepatocellular carcinoma. Overexpression of miR-100 attenuates the invasive and proliferative abilities of hepatocellular carcinoma cells by targeting CXCR7.

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