ArticleMolecular therapy. Nucleic acids2018
Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- LncRNA IRAIN inhibits mantle cell lymphoma progression by inducing cell cycle arrest and apoptosis: an in vitro study.Scientific reports · 2026Article
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- Estrogen-Induced LncRNA, LINC02568, Promotes Estrogen Receptor-Positive Breast Cancer Development and Drug Resistance Through Both In Trans and In Cis Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway.Histology and histopathology · 2022Article
- Decoding Insulin-Like Growth Factor Signaling Pathway From a Non-coding RNAs Perspective: A Step Towards Precision Oncology in Breast Cancer.Journal of mammary gland biology and neoplasia · 2022Review
- Insulin Resistance and Cancer: In Search for a Causal Link.International journal of molecular sciences · 2021Review
- Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.Genome biology · 2021Article
- The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia.Frontiers in cell and developmental biology · 2021Review
- Establishment of a type II insulin-like growth factor receptor gene site-integrated SKBR3 cell line using CRISPR/Cas9.Oncology letters · 2020Article
- lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Comparative transcriptome analysis reveals that PCK1 is a potential gene affecting IMF deposition in buffalo.BMC genomics · 2020Article
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation.Nucleic acids research · 2020Article
- The network of non-coding RNAs and their molecular targets in breast cancer.Molecular cancer · 2020Review
- Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation.Molecular cancer · 2020Article
- miR-100-5p Inhibits Malignant Behavior of Chordoma Cells by Targeting IGF1R.Cancer management and research · 2020Article
- Article
- Long Non-coding RNAFrontiers in oncology · 2020Article
- Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Aberrant insulin-like growth factor I receptor (IGF1R) signaling pathway serves as a well-established target for cancer drug therapy. The intragenic antisense long noncoding RNA (lncRNA) IRAIN, a putative tumor suppressor, is downregulated in breast cancer cells, while IGF1R is overexpressed, leading to an abnormal IGF1R/IRAIN ratio that promotes tumor growth. To precisely target this pathway, we developed an "antisense lncRNA-mediated intragenic cis competition" (ALIC) approach to therapeutically correct the elevated IGF1R/IRAIN bias in breast cancer cells. We used CRISPR-Cas9 gene editing to target the weak promoter of IRAIN antisense lncRNA and showed that in targeted clones, intragenic activation of the antisense lncRNA potently competed in cis with the promoter of the IGF1R sense mRNA. Notably, the normalization of IGF1R/IRAIN transcription inhibited the IGF1R signaling pathway in breast cancer cells, decreasing cell proliferation, tumor sphere formation, migration, and invasion. Using "nuclear RNA reverse transcription-associated trap" sequencing, we uncovered an IRAIN lncRNA-specific interactome containing gene targets involved in cell metastasis, signaling pathways, and cell immortalization. These data suggest that aberrantly upregulated IGF1R in breast cancer cells can be precisely targeted by cis transcription competition, thus providing a useful strategy to target disease genes in the development of novel precision medicine therapies.
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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.