ArticleThe Journal of clinical investigation2016
Reciprocal interplay between thyroid hormone and microRNA-21 regulates hedgehog pathway-driven skin tumorigenesis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Cell-free RNA profiling uncovers non-canonical circulating D2 transcript elevation in Bladder Cancer plasma.The journal of liquid biopsy · 2026Article
- Thyroid hormones and metabolic flexibility: tissue-specific control of energy homeostasis.Frontiers in physiology · 2026Review
- The thyroid hormone activating enzyme, DIO2, is a potential pan-cancer biomarker and immunotherapy target.Journal of endocrinological investigation · 2025Article
- MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome.Biology of sex differences · 2024Article
- αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis.International journal of molecular sciences · 2023Article
- Deiodinases in thyroid tumorigenesis.Endocrine-related cancer · 2023Review
- Type 2 deiodinase is expressed in anaplastic thyroid carcinoma and its inhibition causes cell senescence.Endocrine-related cancer · 2023Article
- Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage.Nature communications · 2023Article
- Thyroid hormones act as modulators of inflammation through their nuclear receptors.Frontiers in endocrinology · 2022Review
- Article
- Thyroid hormone action in epidermal development and homeostasis and its implications in the pathophysiology of the skin.Journal of endocrinological investigation · 2021Review
- Germ Line Mutations in the Thyroid Hormone Receptor Alpha Gene Predispose to Cutaneous Tags and Melanocytic Nevi.Thyroid : official journal of the American Thyroid Association · 2021Article
- Thyroid Hormone Enhances Angiogenesis and the Warburg Effect in Squamous Cell Carcinomas.Cancers · 2021Article
- Deiodinases and Cancer.Endocrinology · 2021Review
- Topical L-thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy?Experimental dermatology · 2020Review
- Article
- Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets.Frontiers in pharmacology · 2020Review
- Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch.Nature communications · 2019Article
- Deiodinases and their intricate role in thyroid hormone homeostasis.Nature reviews. Endocrinology · 2019Review
- Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The thyroid hormone-inactivating (TH-inactivating) enzyme type 3 iodothyronine deiodinase (D3) is an oncofetal protein that is rarely expressed in adult life but has been shown to be reactivated in the context of proliferation and neoplasms. D3 terminates TH action within the tumor microenvironment, thereby enhancing cancer cell proliferation. However, the pathological role of D3 and the contribution of TH metabolism in cancer have yet to be fully explored. Here, we describe a reciprocal regulation between TH action and the cancer-associated microRNA-21 (miR21) in basal cell carcinoma (BCC) skin tumors. We found that, besides being negatively regulated by TH at the transcriptional level, miR21 attenuates the TH signal by increasing D3 levels. The ability of miR21 to positively regulate D3 was mediated by the tumor suppressor gene GRHL3, a hitherto unrecognized D3 transcriptional inhibitor. Finally, in a BCC mouse model, keratinocyte-specific D3 depletion markedly reduced tumor growth. Together, our results establish TH action as a critical hub of multiple oncogenic pathways and provide functional and mechanistic evidence of the involvement of TH metabolism in BCC tumorigenesis. Moreover, our results identify a miR21/GRHL3/D3 axis that reduces TH in the tumor microenvironment and has potential to be targeted as a therapeutic approach to BCC.
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What OpenQuestion holds
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.