ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- The immune sensitivity caused by DUSP11, an RNA 5'-end maturation phosphatase, is adjusted by a human non-coding RNA, nc886.Cellular and molecular life sciences : CMLS · 2025Article
- Non-coding 886 (Epigenetics · 2024Review
- The Versatile Roles of nc886, a Fascinating and Peculiar Regulatory Non-Coding RNA, in Cancer.International journal of molecular sciences · 2024Review
- Role of non‑coding RNAs in UV‑induced radiation effects (Review).Experimental and therapeutic medicine · 2024Review
- Human Vault RNAs: Exploring Their Potential Role in Cellular Metabolism.International journal of molecular sciences · 2024Review
- Single-cell RNA sequencing of nc886, a non-coding RNA transcribed by RNA polymerase III, with a primer spike-in strategy.PloS one · 2024Article
- nc886, an RNA Polymerase III-Transcribed Noncoding RNA Whose Expression Is Dynamic and Regulated by Intriguing Mechanisms.International journal of molecular sciences · 2023Review
- PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents.Molecular therapy. Nucleic acids · 2022Article
- Are We Studying Non-Coding RNAs Correctly? Lessons from nc886.International journal of molecular sciences · 2022Review
- A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus.Molecular therapy oncolytics · 2022Article
- The nuclear and cytoplasmic activities of RNA polymerase III, and an evolving transcriptome for surveillance.Nucleic acids research · 2021Article
- Nc886, a Novel Suppressor of the Type I Interferon Response Upon Pathogen Intrusion.International journal of molecular sciences · 2021Article
- Pan-cancer chromatin analysis of the human vtRNA genes uncovers their association with cancer biology.F1000Research · 2021Article
- LncRNAs in the Type I Interferon Antiviral Response.International journal of molecular sciences · 2020Review
- Characterization of a novel HDAC/RXR/HtrA1 signaling axis as a novel target to overcome cisplatin resistance in human non-small cell lung cancer.Molecular cancer · 2020Article
- vtRNA2-1/nc886 Produces a Small RNA That Contributes to Its Tumor Suppression Action through the microRNA Pathway in Prostate Cancer.Non-coding RNA · 2020Article
- The mystique of epigenetic regulation: the remarkable case of a human noncoding RNA, nc886.EpigenomicsReview
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have discovered a cytotoxic mechanism that involves a cellular noncoding RNA (ncRNA) nc886 and protein kinase R (PKR) that is a proapoptotic protein. nc886 is transcribed by RNA polymerase III (Pol III), binds to PKR, and prevents it from aberrant activation in most normal cells. We have shown here that doxorubicin evicts Pol III from DNA and, thereby, shuts down nc886 transcription. Consequently, the instantaneous depletion of nc886 provokes PKR and leads to apoptosis. In a short-pulse treatment of doxorubicin, these events are the main cause of cytotoxicity preceding the DNA damage response in a 3D culture system as well as the monolayer cultures. By identifying nc886 as a molecular signal for PKR to sense doxorubicin, we have provided an explanation for the conundrum why DNA-damaging drugs can be cytotoxic to quiescent cells that have the competent nc886/PKR pathway.
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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.