ArticleProceedings of the National Academy of Sciences of the United States of America2020
An MXD1-derived repressor peptide identifies noncoding mediators of MYC-driven cell proliferation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- FTO-dependent mInflammation · 2026Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- BARD1-mediated stabilization of METTL14 promotes retinal neovascularization by m6A-modifying MXD1 mRNA on a YTHDF2-dependent manner.Theranostics · 2025Article
- Identifying aging-related biomarkers in adipose tissue using integrative bioinformatics and machine-learning approaches: discovery of ELN, MXD1, and FGF21 as key genes.Frontiers in endocrinology · 2025Article
- Epigenome editing technologies for discovery and medicine.Nature biotechnology · 2024Review
- CRISPRlnc: a machine learning method for lncRNA-specific single-guide RNA design of CRISPR/Cas9 system.Briefings in bioinformatics · 2024Article
- Long Non-Coding RNAs as "MYC Facilitators".Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2.Cell death & disease · 2023Article
- Applications of CRISPR screening to lung cancer treatment.Frontiers in cell and developmental biology · 2023Review
- Strategies to target the cancer driver MYC in tumor cells.Frontiers in oncology · 2023Review
- Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors.eLife · 2022Article
- A Novel CRISPR Interference Effector Enabling Functional Gene Characterization with Synthetic Guide RNAs.The CRISPR journal · 2022Article
- Long Noncoding RNAs and Human Liver Disease.Annual review of pathology · 2022Review
- miRNA- and lncRNA-Based Therapeutics for Non-Hodgkin's Lymphoma: Moving towards an RNA-Guided Precision Medicine.Cancers · 2021Review
- CRISPR-Based Approaches for the High-Throughput Characterization of Long Non-Coding RNAs.Non-coding RNA · 2021Review
- Interrogating lncRNA functions via CRISPR/Cas systems.RNA biology · 2021Review
- Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.Molecular cancer · 2021Review
- Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation.Scientific reports · 2021Article
- Review
- CRISPR/Cas9: Principle, Applications, and Delivery through Extracellular Vesicles.International journal of molecular sciences · 2021Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
MYC controls the transcription of large numbers of long noncoding RNAs (lncRNAs). Since MYC is a ubiquitous oncoprotein, some of these lncRNAs probably play a significant role in cancer. We applied CRISPR interference (CRISPRi) to the identification of MYC-regulated lncRNAs that are required for MYC-driven cell proliferation in the P493-6 and RAMOS human lymphoid cell lines. We identified 320 noncoding loci that play positive roles in cell growth. Transcriptional repression of any one of these lncRNAs reduces the proliferative capacity of the cells. Selected hits were validated by RT-qPCR and in CRISPRi competition assays with individual GFP-expressing sgRNA constructs. We also showed binding of MYC to the promoter of two candidate genes by chromatin immunoprecipitation. In the course of our studies, we discovered that the repressor domain SID (SIN3-interacting domain) derived from the MXD1 protein is highly effective in P493-6 and RAMOS cells in terms of the number of guides depleted in library screening and the extent of the induced transcriptional repression. In the cell lines used, SID is superior to the KRAB repressor domain, which serves routinely as a transcriptional repressor domain in CRISPRi. The SID transcriptional repressor domain is effective as a fusion to the MS2 aptamer binding protein MCP, allowing the construction of a doxycycline-regulatable CRISPRi system that allows controlled repression of targeted genes and will facilitate the functional analysis of growth-promoting lncRNAs.
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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.