ArticleOncogene2022
HOTAIR/Sp1/miR-199a critically regulates cancer stemness and malignant progression of cutaneous squamous cell carcinoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- COL1A1-induced LOXL2 promotes ovarian cancer metastasis via a feedback loop upon inhibiting EGFR lysosomal degradation.Experimental & molecular medicine · 2026Article
- lncRNA HOTAIR in Cancer: Recent Advances and Critical Perspectives on Molecular Mechanisms.Cancer management and research · 2026Review
- A symphony of signals: the intricate role of lncRNAs in dermatological disorders.Clinical and experimental medicine · 2025Review
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- Effect of miR-6767-5p on breast cancer cell phenotype and its regulatory mechanism.Scientific reports · 2025Article
- Long Non-Coding RNAs in Psoriasis and Cutaneous Squamous Cell Carcinoma.Journal of clinical medicine · 2025Review
- Targeted demethylation of the EphA7 promoter inhibits tumorigenesis via the SP1/DNMT1 and PI3K/AKT axes and improves the response to multiple therapies in cervical cancer.Cell death & disease · 2025Article
- Molecular Mechanisms and Therapeutic Implications of Long Non-coding RNAs in Cutaneous Biology and Disease.Journal of cellular physiology · 2025Review
- HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives.Cancer cell international · 2024Review
- Circular RNA NINL accelerates the malignant progression of cervical cancer.Discover oncology · 2024Article
- A concise review of the regulatory, diagnostic, and prognostic implications of HOXB-AS3 in tumors.Journal of Cancer · 2024Review
- Long noncoding RNA MALAT1 in dermatologic disorders: a comprehensive review.Biomarkers in medicine · 2024Review
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
- HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer.Molecular cancer · 2023Review
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- LINC00467: an oncogenic long noncoding RNA.Cancer cell international · 2022Review
- Super Enhancer-RegulatedCancers · 2022Article
- Association between long non-coding RNA HOTAIR polymorphism and lung cancer risk: A systematic review and meta-analysis.Experimental and therapeutic medicine · 2022Article
- Non-coding RNAs in skin cancers:Biological roles and molecular mechanisms.Frontiers in pharmacology · 2022Review
- Investigating Cutaneous Squamous Cell CarcinomaFrontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The long non-coding RNA (lncRNA), HOX antisense intergenic RNA (HOTAIR) is a well-characterized oncogene in multiple human cancers, but not in cutaneous squamous cell carcinoma (CSCC). In this study, we focused on investigating the potential role of HOTAIR in stemness of CSCC. By measuring its expression using RT-qPCR in CSCC vs. normal tissues, as well as in CSCC cell lines A431 or SCC13, A431- or SCC13-derived CSCC stem cells (CSCSCs), and normal skin fibroblasts (HSFs), we detected higher expression of HOTAIR in CSCC than in normal tissues, in recurrent than in non-recurrent CSCC tissues, in CSCCs and CSCSCs than in HSFs, and particularly, in CSCSCs than in CSCCs. Kaplan-Meier analysis suggested that higher expression of HOTAIR was positively correlated with worse overall survival of CSCC patients. Functional assays on colony formation, EdU incorporation, sphere formation, western blot on stem-cell biomarkers, and in vivo models showed that HOTAIR was essential in maintaining multiple stem cell phenotypes of CSCSCs in vitro and in vivo xenograft growth as well as metastasis. Mechanistically, HOTAIR directly interacted with and up-regulated Sp1. Sp1 then induced DNMT1-mediated promoter methylation and direct transcriptional repression of miR-199a-5p. Targeting Sp1 or DNMT1 further boosted the in vivo anti-tumor and anti-metastasis activities of targeting HOTAIR. In conclusion, HOTAIR, by up-regulating Sp1 and targeting miR-199a, promotes stemness and progression of CSCC. Targeting HOTAIR, Sp1 or the underlying mechanisms may thus benefit CSCC treatment.
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