Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma cells.

Manya Wu,Haixia Li,Caifu Zhou,Xiaoyun Shen,Yanping Tang,Xiaoling Luo

doi:10.7717/peerj.8624

Manya Wu, Haixia Li + Show 4 more

Open Access

https://doi.org/10.7717/peerj.8624

Copy DOI

Journal: PeerJ	Publication Date: Feb 26, 2020
Citations: 3	License type: CC BY 4.0

Affiliation: Guangxi Medical University, Sir Run Run Shaw Hospital

Abstract

As the first-line treatment, sorafenib has been used for advanced hepatocellular carcinoma (HCC), but the chemoresistance commonly restricts to the clinical efficiency. In this study, we intend to investigate the genome-wide expression pattern of long noncoding RNAs (lncRNAs) in sorafenib-resistant HCC. Herein, we identified thousands of differentially expressed lncRNAs in sorafenib-resistant HCC cells by high-throughput sequencing compared to the parental. Besides, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the sorafenib-resistant Huh7 cells (Huh7-S) and sorafenib-resistant HepG2 cells (HepG2-S) compared to the parental cells. Moreover, when analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, the differentially expressed genes were significantly related to the tight junction. Among them, the expression of TCONS_00284048 and TCONS_00006019 was consistently up-regulated in sorafenib-resistant HCC cell lines, whereas when either was knocked down, the sensitivity of Huh7-S and HepG2-S cells to sorafenib was increased. Taken together, our data demonstrate that the lncRNA expression profile is significantly altered in sorafenib-resistant HCC cells as well as differentially expressed lncRNAs may play crucial functions on HCC sorafenib resistance and HCC progression.

Highlights

With more than 780,000 deaths annually, hepatocellular carcinoma (HCC) is the fourth main cause of cancer death globally (Bray et al, 2018)
IC50 values were to determine the efficacy of sorafenib resistance in Huh7 and HepG2 cells
The values IC50 were significantly higher in sorafenib resistant cell lines, with Huh7-S cells (IC50 = 5.73 ± 0.23 μM) showing a 3.24-fold increased resistance to sorafenib compared to parental Huh7 cells (IC50 = 1.77 ± 0.35 μM; p = 0.0001) (Fig. 1A) and HepG2-S cells (IC50 = 27.09 ± 1.73 μM) showing a 2.38-fold increased resistance compared to parental HepG2 cells (IC50 = 11.36 ± 0.66 μM; p = 0.0001) (Fig. 1B)

Summary

Introduction

With more than 780,000 deaths annually, HCC is the fourth main cause of cancer death globally (Bray et al, 2018). Though surgical resection is still the preferred method for the treatment of liver cancer, most of patients are at the advanced stage of disease at the time of diagnosis and are unsuitable for resection. As an oral multi-kinase inhibitor, is the unique molecular targeted drug used to treat with advanced HCC patients, for whom. How to cite this article Wu M, Shen X, Tang Y, Zhou C, Li H, Luo X. Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma cells. Sorafenib-treated patients have been demonstrated with an increased median survival time (Cheng et al, 2009; Llovet et al, 2008), the high level of resistant rate has limited the efficiency of sorafenib therapy significantly

Methods

Results

Discussion

Conclusion