Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer

Zhang, Youyou; He, Qun; Hu, Zhongyi; Feng, Yi; Fan, Lingling; Tang, Zhaoqing; Yuan, Jiao; Shan, Weiwei; Li, Chunsheng; Hu, Xiaowen; Tanyi, János L.; Fan, Yi; Huang, Qihong; Montone, Kathleen T.; Dang, Chi V.; Zhang, Lin

doi:10.1038/nsmb.3211

Cited by 246 publications

(242 citation statements)

References 40 publications

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“…Alternatively, CUPID1 might be acting as an RNA scaffold for DNA-repair complexes similarly to LINP1, which has recently been shown to promote NHEJ by acting as a RNA scaffold for Ku70-Ku80 and DNA-PKcs. 35 In summary, we have shown that breast cancer risk variants at 11q13 might regulate two lncRNAs, in addition to CCND1, and provide evidence that reduced expression of the lncRNAs mediates risk by favoring a switch from HRR to NHEJ DSB repair. Importantly, these data are consistent with observations in breast tumors whereby a HR mutation signature is associated with increased structural variants presumably caused by DSB repair through error-prone pathways.…”

Section: Discussionmentioning

confidence: 66%

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Betts

Marjaneh

Al-Ejeh

et al. 2017

The American Journal of Human Genetics

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Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

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Section: Discussionmentioning

confidence: 66%

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Betts

Marjaneh

Al-Ejeh

et al. 2017

The American Journal of Human Genetics

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“…Our results were consistent with the expression trends of the sequencing data. LINP1 significantly overexpressed in basal breast cancer and regulated repair of DNA breaks [19]. LINC01011 expressed differentially in intrahepatic cholangiocarcinoma and adjacent normal tissues [20].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

Cao

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. Methods: We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. Results: We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. Conclusion: Our findings revealed the significant role of lncRNAs in the development process of bladder cancer.

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“…Critical to NHEJ function is protein phosphorylation by both DNA-PKcs and the related ATM, which phosphorylate each other and other components of the DDR to regulate NHEJ and other cellular processes. Recently, noncoding RNAs have also been shown to regulate DSB repair (Lees-Miller, Beattie, & Tainer, 2016; Zhang et al, 2016), adding an additional level of largely unexplored regulation to the system.…”

Section: Dna Double-strand Break Responsesmentioning

confidence: 99%

What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses

Brosey

Ahmed

Lees‐Miller

et al. 2017

Methods in Enzymology

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DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered. In this chapter, we discuss concepts and strategies for combining structural, biophysical, and imaging techniques to investigate DDR recognition and regulation, and thus bridge sequence-level structural biochemistry to quantitative biological outcomes visualized in cells. We focus on representative DDR responses from PARP/PARG/AIF damage signaling in DNA single-strand break repair and nonhomologous end joining complexes in double-strand break repair. Methods with exemplary experimental results are considered with a focus on strategies for probing flexibility, conformational changes, and assembly processes that shape a predictive understanding of DDR mechanisms in a cellular context. Integration of structural and imaging measurements promises to provide foundational knowledge to rationally control and optimize DNA damage outcomes for synthetic lethality and for immune activation with resulting insights for biology and cancer interventions.

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Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer

Cited by 246 publications

References 40 publications

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses

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