ArticleThe Journal of clinical investigation2011
A microRNA-dependent program controls p53-independent survival and chemosensitivity in human and murine squamous cell carcinoma.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Strategies for Anticancer Treatment in p53-Mutated Head and Neck Squamous Cell Carcinoma.Biomedicines · 2025Article
- The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway.Cancers · 2022Review
- P63 and P73 Activation in Cancers with p53 Mutation.Biomedicines · 2022Review
- The Roles of microRNAs in Cancer Multidrug Resistance.Cancers · 2022Review
- Article
- Oh, the Mutations You'll Acquire! A Systematic Overview of Cutaneous Squamous Cell Carcinoma.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Enhancement of myogenic differentiation and inhibition of rhabdomyosarcoma progression by miR-28-3p and miR-193a-5p regulated by SNAIL.Molecular therapy. Nucleic acids · 2021Article
- The p53 family reaches the final frontier: the variegated regulation of the dark matter of the genome by the p53 family in cancer.RNA biology · 2020Article
- Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer.Journal of the National Cancer Institute · 2020Article
- Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis.International journal of molecular sciences · 2019Review
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
- The role and mechanisms of action of microRNAs in cancer drug resistance.Clinical epigenetics · 2019Review
- MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer.BMC cancer · 2018Article
- Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression.Frontiers in genetics · 2018Article
- Article
- Review
- MiR-491-5p negatively regulates cell proliferation and motility by targeting PDGFRA in prostate cancer.American journal of cancer research · 2017Article
- miRNA-193a-5p repression of p73 controls Cisplatin chemoresistance in primary bone tumors.Oncotarget · 2016Article
- Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer.Scientific reports · 2016Article
- ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFβ-Induced Metastasis.Cancer research · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The p53 tumor suppressor, a central mediator of chemosensitivity in normal cells, is functionally inactivated in many human cancers. Therefore, a central challenge in human cancer therapy is the identification of pathways that control tumor cell survival and chemosensitivity in the absence of functional p53. The p53-related transcription factors p63 and p73 exhibit distinct functions—p73 mediates chemosensitivity while p63 promotes proliferation and cell survival—and are both overexpressed in squamous cell carcinomas (SCCs). However, how p63 and p73 interact functionally and govern the balance between prosurvival and proapoptotic programs in SCC remains elusive. Here, we identify a microRNA-dependent mechanism of p63/p73 crosstalk that regulates p53-independent survival of both human and murine SCC. We first discovered that a subset of p63-regulated microRNAs target p73 for inhibition. One of these, miR-193a-5p, expression of which was repressed by p63, was activated by proapoptotic p73 isoforms in both normal cells and tumor cells in vivo. Chemotherapy caused p63/p73-dependent induction of this microRNA, thereby limiting chemosensitivity due to microRNA-mediated feedback inhibition of p73. Importantly, inhibiting miR-193a interrupted this feedback and thereby suppressed tumor cell viability and induced dramatic chemosensitivity both in vitro and in vivo. Thus, we have identified a direct, microRNA-dependent regulatory circuit mediating inducible chemoresistance, whose inhibition may provide a new therapeutic opportunity in p53-deficient tumors.
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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.