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Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Abstract：

:Sorafenib may provide survival benefits for patients with advanced hepatocellular carcinoma. However, tumor cells can display primary or secondary resistance to Sorafenib. To identify genes capable of conveying Sorafenib resistance, we performed a genome-wide CRISPR transcriptional activation library (SAM) in human Huh7 cells. We identified that a group of sgRNAs were significantly enriched in Sorafenib resistant Huh7 cells, which indicated that these sgRNAs up-regulated their target genes and induced resistance. We finally identified LRP8 as a key gene that can drive HCC cell to acquire sorafenib resistance. All three sgRNAs targeting LRP8 were identified in Sorafenib resistant Huh7 cells with high copy. We also showed that sorafenib-acquired resistant Huh7 cells have much higher LRP8 expression level than parental Huh7 cells. We proved that overexpression of LRP8 in HCC cell lines activated β-catenin and significantly promoted its resistance to Sorafenib. We further showed that overexpression of LRP8 reduced the apoptosis level of HCC cell lines. To summary, genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Cai J,Chen J,Wu T,Cheng Z,Tian Y,Pu C,Shi W,Suo X,Wu X,Zhang K

doi

10.1016/j.bbrc.2020.04.040

subject

Has Abstract

pub_date

2020-06-11 00:00:00

pages

1170-1176

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)30766-X

journal_volume

526

pub_type

杂志文章

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