ArticleCell death & disease2015
Long noncoding RNA lincRNA-p21 is the major mediator of UVB-induced and p53-dependent apoptosis in keratinocytes.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 120 citations in OpenAlex.
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- Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases.Frontiers in oncology · 2025Review
- Antitumor Effects of Sesamin via the LincRNA-p21/STAT3 Axis in Human Bladder Cancer: Inhibition of Metastatic Progression and Enhanced Chemosensitivity.International journal of biological sciences · 2025Article
- Long non-coding RNAs: roles in cellular stress responses and epigenetic mechanisms regulating chromatin.Nucleus (Austin, Tex.) · 2024Review
- Role of non‑coding RNAs in UV‑induced radiation effects (Review).Experimental and therapeutic medicine · 2024Review
- Converting "cold" to "hot": epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells.Cancer communications (London, England) · 2024Review
- p53-regulated lncRNAs in cancers: from proliferation and metastasis to therapy.Cancer gene therapy · 2023Review
- LncRNA RARA-AS1 could serve as a novel prognostic biomarker in pan-cancer and promote proliferation and migration in glioblastoma.Scientific reports · 2023Article
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- Modulating epigenetic modifications for cancer therapy (Review).Oncology reports · 2023Review
- TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma.Cancer informatics · 2023Article
- The role of lincRNA-p21 in regulating the biology of cancer cells.Human cell · 2022Review
- Notch-associated lncRNAs profiling circuiting epigenetic modification in colorectal cancer.Cancer cell international · 2022Review
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- Non-coding RNAs in photoaging-related mechanisms: a new paradigm in skin health.Biogerontology · 2022Review
- Stressing the Regulatory Role of Long Non-Coding RNA in the Cellular Stress Response during Cancer Progression and Therapy.Biomedicines · 2022Review
- Downregulation of long non-coding RNAs in patients with bipolar disorder.Scientific reports · 2022Article
- Regulation of Oxidative Stress by Long Non-coding RNAs in Central Nervous System Disorders.Frontiers in molecular neuroscience · 2022Review
- Tubule-specific deletion ofMolecular therapy. Nucleic acids · 2021Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
LincRNA-p21 is a long noncoding RNA and a transcriptional target of p53 and HIF-1α. LincRNA-p21 regulates gene expression in cis and trans, mRNA translation, protein stability, the Warburg effect, and p53-dependent apoptosis and cell cycle arrest in doxorubicin-treated mouse embryo fibroblasts. p53 plays a key role in the response of skin keratinocytes to UVB-induced DNA damage by inducing cell cycle arrest and apoptosis. In skin cancer development, UVB-induced mutation of p53 allows keratinocytes upon successive UVB exposures to evade apoptosis and cell cycle arrest. We hypothesized that lincRNA-p21 has a key functional role in UVB-induced apoptosis and/or cell cycle arrest in keratinocytes and loss of lincRNA-p21 function results in the evasion of apoptosis and/or cell cycle arrest. We observed that lincRNA-p21 transcripts are highly inducible by UVB in mouse and human keratinocytes in culture and in mouse skin in vivo. LincRNA-p21 is regulated at the transcriptional level in response to UVB, and the UVB induction of lincRNA-p21 in keratinocytes and in vivo in mouse epidermis is primarily through a p53-dependent pathway. Knockdown of lincRNA-p21 blocked UVB-induced apoptosis in mouse and human keratinocytes, and lincRNA-p21 was responsible for the majority of UVB-induced and p53-mediated apoptosis in keratinocytes. Knockdown of lincRNA-p21 had no effect on cell proliferation in untreated or UVB-treated keratinocytes. An early event in skin cancer is the mutation of a single p53 allele. We observed that a mutant p53(+/R172H) allele expressed in mouse epidermis (K5Cre(+/tg);LSLp53(+/R172H)) showed a significant dominant-negative inhibitory effect on UVB-induced lincRNA-p21 transcription and apoptosis in epidermis. We conclude lincRNA-p21 is highly inducible by UVB and has a key role in triggering UVB-induced apoptotic death. We propose that the mutation of a single p53 allele provides a pro-oncogenic function early in skin cancer development through a dominant inhibitory effect on UVB-induced lincRNA-p21 expression and the subsequent evasion of UVB-induced apoptosis.
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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.