Single cell RNA-seq analysis identifies a noncoding RNA mediating resistance to sorafenib treatment in HCC

Despite showing upregulation of stemness/EMT genes, Huh7-R cells showed downregulation of the proliferative marker MKI67, and cell-cycle related genes (Fig. 1E) suggesting that sorafenib treatment may enrich a subset of resistant cells with slow cell cycle or those that lie in a dormant state. Surpr...

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Bibliographic Details
Published in:	Molecular cancer 2022-01, Vol.21 (1), p.6-6, Article 6
Main Authors:	Zhou, Kevin, Nguyen, Romario, Qiao, Liang, George, Jacob
Format:	Article
Language:	eng
Subjects:	Analysis Antisense RNA Biomarkers, Tumor Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - genetics Cell cycle Datasets Development and progression Drug approval Drug resistance Drug Resistance, Neoplasm - genetics Drug therapy Epithelial-Mesenchymal Transition Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Kinases Letter to the Editor Ligands Liver cancer Liver Neoplasms - diagnosis Liver Neoplasms - drug therapy Liver Neoplasms - genetics Proteins RNA, Long Noncoding Single-Cell Analysis Sorafenib - pharmacology Sorafenib - therapeutic use Stem cells Transcriptome Tumors
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Summary:	Despite showing upregulation of stemness/EMT genes, Huh7-R cells showed downregulation of the proliferative marker MKI67, and cell-cycle related genes (Fig. 1E) suggesting that sorafenib treatment may enrich a subset of resistant cells with slow cell cycle or those that lie in a dormant state. Surprisingly, these rare Huh7-P cells (named as candidate stem cells) showed gene expression signatures with great similarity to that of Huh7-R cells (Fig. 1G) suggesting that drug-resistant cells with stemness/EMT traits may have pre-existed in the naïve cells and become prevalent following long-term sorafenib exposure. In this analysis, we found that ZFAS1 expression was significantly upregulated in HCC and recurrent tumours compared with that of matching normal liver by using the GEPIA dataset (Supplementary Fig. 3B) and the University of California Santa Cruz (UCSC) Xena project (http://xena.ucsc.edu) (Supplementary Fig. 3C). [...]ZFAS1 was overexpressed at higher stages (III/IV) of HCC and in poorly (G3)/undifferentiated HCC (G4) compared with those at early stages (I/II) (Supplementary Fig. 3D) and in highly (G1)/moderately (G2) differentiated HCC (Supplementary Fig. 3E). [...]killing quiescent cancer stem-like cells might be a strategy to overcome sorafenib resistance.
ISSN:	1476-4598 1476-4598