Global transcriptomic study of circRNAs expression profile in sorafenib resistant hepatocellular carcinoma cells

Abstract

The anti-angiogenic drugs represented by sorafenib over the years have always been the first-line treatment of hepatocellular carcinoma (HCC), but the drug resistance has always been a "bottleneck" in curative effect. Recently, aberrant expression of circular RNA (circRNA) is considered to play a crucial role in many types of cancers. However, the genome-wide expression pattern of circRNAs in sorafenib-resistant HCC cells remains unknown. Herein, we identified 1717 differentially expressed circRNAs with 559 up-regulated and 1158 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HUH7-S) HCC cells along with 582 differentially expressed circRNAs with 272 up-regulated and 310 down-regulated (fold change > 2, P < 0.05) in sorafenib-resistant (HepG2-S) HCC cells, compared to parental sorafenib-sensitive (HUH7, HepG2) HCC cells by high-throughput sequencing. In addition, GO (Gene Ontology) term enrichment analysis results revealed an enrichment for binding and catalytic activity and for biological regulation of metabolic processes in both the Huh7-S and HepG2-S cell lines compared to parental cell lines. Moreover, KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway analysis of the differentially expressed genes were significantly related to pathways in cancer. Among them, hsa_circ_0006294 and hsa_circ_0035944 expression were consistently down-regulated in resistant HCC cells. Taken together, our data demonstrate, using a global transcriptomic network, that the circRNA expression profile is significantly altered in sorafenib-resistant HCC cells and that the differentially expressed circRNAs may play important functions in HCC sorafenib resistance and HCC progression.

Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs

“…4 d, e) were chosen for further validation. Among these circRNA candidates, approximately half of them were upregulated in sorafenib-resistant Huh7 cells according to the previously published RNA-seq data [ 25 ] (Additional file 1 : Figure S8d). The circular structure of these circRNA candidates was confirmed by RNase R treatment (Additional file 1 : Figure S8e).…”

“…However, resistance to sorafenib frequently occurs and limits the benefit of such therapeutic option. Recently, genome-wide expression pattern of circRNAs in sorafenib-resistant HCC cells has been analyzed, and over 1000 differentially expressed circRNAs have been identified [ 25 ], indicating a potential role of circRNAs in the development of sorafenib resistance. To test this hypothesis, we performed drug selection screening with the larger Cas13d library to identify circRNAs, whose inhibition could increase the therapeutic efficacy of sorafenib in Huh7 cells (Fig.…”

Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis

“… 4 Some circRNAs have been recently identified as important regulators in HCC chemoresistance by functioning as sponges of microRNAs (miRNAs). 5 Li et al showed that circRNA F-box protein 11 (circFBXO11) enhanced oxaliplatin resistance of HCC by sequestering miR-605. 6 Luo et al demonstrated that circ_101505 regulated HCC cell resistance to cisplatin (DDP) by working as a miR-103 sponge.…”

Comprehensive Analysis of Differentially Expressed circRNAs Reveals a Colorectal Cancer-Related ceRNA Network

“…Of note, some of these circRNAs had been demonstrated to be related to cancer progression. For example, hsa_circ_0084663 was validated to be related to sorafenib-resistant liver cancer [ 42 ]. Very interestingly, we found that hsa_circ_0061776 and hsa_circ_0006528 were also upregulated in colon samples by analyzing the supplementary table in an independent report [ 25 ].…”