Accession

PRJCA004744

Title

CRISPR screen identifies CDK12 as conservative vulnerability of prostate cancer

Relevance

Medical

Data types

Epigenomics
Transcriptome or Gene expression
Raw sequence reads

Organisms

Homo sapiens

Description

We used CRISPR screen and identified CDK12 as conservatively required for survival of PCa cells both under normal and AR antagonism stress. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. THZ531 downregulated AR signaling, and preferentially repressed a distinct class of CDK12-inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes and contributing to survival processes of PCa cells. Integration of super-enhancers (SEs) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, and their downregulation may further explain the anti-PCa properties. Moreover, CDK12 inhibition strikingly synergized AR antagonists with significantly attenuated H3K27ac signal on AR targets and intensive SE-associated apoptosis pathway.

Sample scope

Monoisolate

Release date

2021-07-24

Grants

Agency	program	Grant ID	Grant title
National Natural Science Foundation of China (NSFC)		81772754
National Natural Science Foundation of China (NSFC)		81820108024
National Natural Science Foundation of China (NSFC)		81630005
National Natural Science Foundation of China (NSFC)		81773166
the Major Basic Research and Cultivation Program of Natural Science Foundation of Guangdong Province		2017A03038009
the Shenzhen Basic Science Research		JCYJ20190809164617205
the Sanming Project of Medicine in Shenzhen		SZSM202011011
the Research start-up fund of part-time PI, SAHSYSU		ZSQYJZPI202003
the National Key R&D Program of China		2019YFA0110300
the National Key R&D Program of China		2017YFA0505600-04
the Science and Technology Planning Project of Guangzhou		201804020044

Submitter

Jun Pang (pangjun2@mail.sysu.edu.cn)

Organization

the Seventh Affiliated Hospital of the Sun Yat-Sen University, Shenzhen, Guangdong, China

Submission date

2021-03-18

Project Data

Resource name	Description
BioSample (21) show	-
SAMC1648658	CRISPR screen
SAMC1648652	ChIP-seq-CUT&Tag
SAMC1648648	ChIP-seq-CUT&Tag
SAMC1648644	ChIP-seq-CUT&Tag
SAMC1648641	ChIP-seq-CUT&Tag
SAMC1648636	ChIP-seq-CUT&Tag
SAMC1648632	ChIP-seq-CUT&Tag
SAMC1648628	ChIP-seq-CUT&Tag
SAMC1648621	ChIP-seq-CUT&Tag
SAMC1648614	RNA-seq
SAMC1648610	RNA-seq
SAMC1648605	RNA-seq
SAMC1648598	RNA-seq
SAMC1648592	RNA-seq
SAMC1648587	RNA-seq
SAMC1648580	RNA-seq
SAMC1648578	RNA-seq
SAMC1648573	RNA-seq
SAMC1648567	RNA-seq
SAMC1648562	RNA-seq
SAMC1648555	RNA-seq