Evidence map›Paper›PMID 42754663›Full record

ArticleOncogene2026

CRISPR/Cas9 screening revealed BIRC6-AS1/BIRC6 mediates abiraterone resistance via NHEJ pathway-dependent A20 degradation in prostate cancer.

Lan Li, Xue-Ni An, Yong-Tong Ruan, Rong Yang, Peng Li, Pei-Tong Shen, Han-Yu Zeng, Xiao-Yu Wu, Xian-Chao Huang, Ming-Yuan Song and 3 more

Abstract read
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In one paragraph

Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Lan LiCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Xue-Ni AnCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Yong-Tong RuanCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Rong YangCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Peng LiCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Pei-Tong ShenCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Han-Yu ZengCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Xiao-Yu WuCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Xian-Chao HuangCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Ming-Yuan SongCollege of Life Sciences, Shaanxi Normal University, Xi'an, China.
Jing-Lan HaoCollege of Life Sciences, Shaanxi Normal University, Xi'an, China. jlhao1128@163.com.ORCID http://orcid.org/0000-0001-6490-2271
Ping GaoCollege of Life Sciences, Shaanxi Normal University, Xi'an, China. ping.gao2016@outlook.com.ORCID http://orcid.org/0000-0003-1383-3290
Xiao-Ming DongCollege of Life Sciences, Shaanxi Normal University, Xi'an, China. dongxm2008duzhe@126.com.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82472665Natural Science Foundation of Shaanxi Province (Shaanxi Province Natural Science Foundation) 2023-JC-YB-716
6 · The paper itself

Abstract

Abiraterone acetate is a standard-of-care therapy for prostate cancer (PCa). However, resistance frequently emerges, often characterized by the progression to AR-independent phenotypes. Employing a genome-wide CRISPR/Cas9 library screening strategy, we identified 523 long non-coding RNAs (lncRNAs) and 2,183 protein-coding genes as potential candidates associated with abiraterone resistance. Notably, a pair of sense-antisense genes, BIRC6-AS1/BIRC6, was identified as a significant contributor to abiraterone resistance, serving as a critical survival factor in AR-independent contexts. BIRC6-AS1 depletion led to a reduction in both the mRNA and protein levels of BIRC6. Moreover, depletion of either BIRC6-AS1 or BIRC6 enhanced the sensitivity of PCa cells to abiraterone in both in vitro and in vivo settings. Further investigation revealed that BIRC6-AS1 stabilized the mRNA of BIRC6 through interaction with ILF2. Suppression of either BIRC6-AS1 or BIRC6 attenuated non-homologous end joining (NHEJ) repair activity, resulting in the disassembly of 53BP1 foci at DNA damage sites and an increased accumulation of DNA damage, thereby exposing a vulnerability in AR-independent resistant cells. Mechanistically, BIRC6 interacted with A20 and facilitated the K48-linked ubiquitination and subsequent degradation of A20 at the K337 residue. Additionally, A20 knockdown effectively reversed the abiraterone sensitivity induced by BIRC6-AS1 depletion. Collectively, our study provides a landscape of lncRNAs and protein-coding genes associated with abiraterone resistance and suggests that targeting the BIRC6-AS1/BIRC6 axis represents a potential therapeutic strategy to eradicate AR-independent resistant tumors in prostate cancer.

Identifiers

PMID42754663

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