Dataset Information

Long non?coding RNA H19 is involved in sorafenib resistance in hepatocellular carcinoma by upregulating miR?675.

ABSTRACT: Sorafenib is the first?line treatment for advanced hepatocellular carcinoma (HCC). Since many HCC patients experience drug resistance, there is an urgent need to discover more effective therapeutic strategies to overcome drug resistance. Long non?coding RNAs (lncRNAs) play an important role in tumor drug resistance. However, research on the role of lncRNA H19 in sorafenib resistance in HCC is quite limited. In the present study, CCK?8 assay, RT?qPCR, EdU staining, immunofluorescence staining, and western blot analysis were used to detect the effect of lncRNA H19 on sorafenib resistance of HCC cells. H19 expression was found to be negatively related to sorafenib sensitivity in HCC cells. Knockdown of lncRNA H19 elevated sorafenib sensitivity by suppressing epithelial?mesenchymal transition (EMT) in HCC cells. H19 upregulated miR?675 expression. miR?675 inhibitor decreased the cell viability in sorafenib?treated HCC cells, while miR?675 overexpression had the opposite effect on the treated cells. When the cells were pretreated with miR?675 mimic, H19 siRNA did not alter the effect of miR?675 on sorafenib sensitivity. In conclusion, our study provides new clues for further clinical treatment of sorafenib?resistant liver cancer patients.

SUBMITTER: Xu Y

PROVIDER: S-EPMC7251775 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long non‑coding RNA H19 is involved in sorafenib resistance in hepatocellular carcinoma by upregulating miR‑675.

Xu Yongzi Y Liu Yanhui Y Li Zhenrong Z Li Hao H Li Xiqing X Yan Lei L Mao Jiayan J Shen Jian J Chen Wei W Xue Fei F

Oncology reports 20200508 1

Sorafenib is the first‑line treatment for advanced hepatocellular carcinoma (HCC). Since many HCC patients experience drug resistance, there is an urgent need to discover more effective therapeutic strategies to overcome drug resistance. Long non‑coding RNAs (lncRNAs) play an important role in tumor drug resistance. However, research on the role of lncRNA H19 in sorafenib resistance in HCC is quite limited. In the present study, CCK‑8 assay, RT‑qPCR, EdU staining, immunofluorescence staining, an ...[more]

PMID: 32627034

Similar Datasets

Project description:BackgroundHepatocellular carcinoma (HCC) is a challenging malignancy of global importance, it is the third most common cause of cancer-related mortality worldwide. In the last years the multikinase inhibitor sorafenib has been used for advanced HCC, but some patients do not benefit from this therapy; thus, novel therapeutic options based on molecular approaches are urgently needed. microRNAs are short non coding RNAs involved in several physiological and pathological conditions including HCC and increasing evidence describes miRs as good tools for the molecular targeted therapies in HCC. The purpose of this study was to identify novel approaches to sensitize the HCC cells to sorafenib by microRNAs targeting urokinase-type plasminogen activator (uPA).MethodsThe miR-193a was validated as negative regulator of urokinase-type plasminogen activator (uPA) in 2 HCC undifferentiated cell lines by transient transfection of miR and anti-miR molecules. The molecular interaction between miR-193a and uPA mRNA target was verified by luciferase reporter assay. The miR-193a expression level was evaluated by stem-loop real time PCR in tumoral tissues from 39 HCC patients. The HCC cells were co-treated with sorafenib and miR-193a and the effects on cellular proliferation, apoptosis were tested. The effect of sorafenib on c-met expression levels was assessed by western blotting.ResultsThe miR-193a has resulted a negative regulator of uPA in both the HCC cell lines tested. The miR-193a expression has resulted dysregulated in tumoral tissues from 39 HCC patients. We found miR-193a down-regulation in HCC respect to peritumoral (PT) tissues and more in the cirrhotic HCCs than in non-cirrhotic ones. Transfection of HA22T/VGH HCC cells with miR-193a decreased proliferation and increased apoptosis, and combined treatment with miR-193a and sorafenib led to further proliferation inhibition.ConclusionsOur results present new advances in the post-transcriptional miR-mediated mechanisms of uPA and they suggest a new strategy to impair the aggressive behavior of HCC cells. Our findings could be helpful to explore novel approaches for multi-target and multi-agent therapies of the HCC.

Dataset Information

Long non?coding RNA H19 is involved in sorafenib resistance in hepatocellular carcinoma by upregulating miR?675.

Publications

Long non‑coding RNA H19 is involved in sorafenib resistance in hepatocellular carcinoma by upregulating miR‑675.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets