ArticlePLoS biology2020
A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Mapping the non-coding RNA landscape in ataxia telangiectasia: a scoping review of ATM dependent miRNA and lncRNA dysregulation.Molecular biology reports · 2025Article
- LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms.Biomolecules · 2025Review
- LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma.Cell death & disease · 2024Article
- Regulatory RNAs: role as scaffolds assembling protein complexes and their epigenetic deregulation.Exploration of targeted anti-tumor therapy · 2024Review
- ATR-binding lncRNA ScaRNA2 promotes cancer resistance through facilitating efficient DNA end resection during homologous recombination repair.Journal of experimental & clinical cancer research : CR · 2023Article
- Long noncoding RNA HITT coordinates with RGS2 to inhibit PD-L1 translation in T cell immunity.The Journal of clinical investigation · 2023Article
- Long Non-Coding RNAs as Epigenetic Regulators of Immune Checkpoints in Cancer Immunity.Cancers · 2022Review
- Mechanistic Contributions of lncRNAs to Cellular Signaling Pathways Crucial to the Lifecycle of Human Papillomaviruses.Viruses · 2022Review
- Long non‑coding RNAs interact with RNA‑binding proteins to regulate genomic instability in cancer cells (Review).Oncology reports · 2022Review
- Review
- Stressing the Regulatory Role of Long Non-Coding RNA in the Cellular Stress Response during Cancer Progression and Therapy.Biomedicines · 2022Review
- Establishment and validation of a prognostic model based on HRR-related lncRNAs in colon adenocarcinoma.World journal of surgical oncology · 2022Article
- lncRNA HITT inhibits metastasis by attenuating Rab5-mediated endocytosis in lung adenocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury.Life (Basel, Switzerland) · 2022Article
- lncRNA HITT Inhibits Lactate Production by Repressing PKM2 Oligomerization to Reduce Tumor Growth and Macrophage Polarization.Research (Washington, D.C.) · 2022Article
- Molecular mechanisms of long noncoding RNAs associated with cervical cancer radiosensitivity.Frontiers in genetics · 2022Review
- Home and Away: The Role of Non-Coding RNA in Intracellular and Intercellular DNA Damage Response.Genes · 2021Review
- The evolving complexity of DNA damage foci: RNA, condensates and chromatin in DNA double-strand break repair.DNA repair · 2021Review
- Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies.Cancers · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ataxia-telangiectasia mutated (ATM) is an apical kinase of the DNA damage response following DNA double-strand breaks (DSBs); however, the mechanisms of ATM activation are not completely understood. Long noncoding RNAs (lncRNAs) are a class of regulatory molecules whose significant roles in DNA damage response have started to emerge. However, how lncRNA regulates ATM activity remains unknown. Here, we identify an inhibitor of ATM activation, lncRNA HITT (HIF-1α inhibitor at translation level). Mechanistically, HITT directly interacts with ATM at the HEAT repeat domain, blocking MRE11-RAD50-NBS1 complex-dependent ATM recruitment, leading to restrained homologous recombination repair and enhanced chemosensitization. Following DSBs, HITT is elevated mainly by the activation of Early Growth Response 1 (EGR1), resulting in retarded and restricted ATM activation. A reverse association between HITT and ATM activity was also detected in human colon cancer tissues. Furthermore, HITTs sensitize DNA damaging agent-induced cell death both in vitro and in vivo. These findings connect lncRNA directly to ATM activity regulation and reveal potential roles for HITT in sensitizing cancers to genotoxic treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.