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The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous
Yixuan Zhao1, Xin Huang1, Zewei Zhang1,2
1Department of Plastic and Reconstructive Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Head and neck squamous carcinoma (HNSC) is the most prevalent malignancy of the head and neck regions. Long noncoding RNAs (lncRNAs) are vital in tumorigenesis regulation. However, the role of lncRNAs in HNSC requires further exploration. Herein, through bioinformatic assays using The Cancer Genome Atlas (TCGA) datasets, rapid amplification of cDNA ends (RACE) assays, and RNA-FISH, we revealed that a novel cytoplasmic transcript, HNSC-associated transcript 1 (HNSCAT1, previously recognized as linc01269), was downregulated in tumor samples and advanced tumor stages and was also associated with favorable outcomes in HNSC. Overexpression of HNSCAT1 triggered treatment efficacy in HNSCs both in vivo and in vitro. More importantly, through high-throughput transcriptome analysis (RNA-seq, in NODE database, OEZ007550), we identified KRT80, a tumor suppressor in HNSC, as the target of HNSCAT1. KRT80 expression was modulated by lncRNA HNSCAT1 and presented a positive correlation in tumor samples (R = 0.52, p < 0.001). Intriguingly, we identified that miR-1245 simultaneously interacts with KRT80 and HNSCAT1, which bridges the regulatory function between KRT80 and HNSCAT1. Conclusively, our study demonstrated that lncRNA HNSCAT1 functions as a necessary tumor inhibitor in HNSC, which provides a novel mechanism of lncRNA function and provides alternative targets for the diagnosis and treatment of HNSC.
Insights
Head and neck squamous cell carcinoma (HNSC) is inhibited by HNSC-associated transcript 1 (HNSCAT1). This novel long noncoding RNA (lncRNA) targets KRT80, offering potential diagnostic and therapeutic strategies for HNSC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Head and neck squamous cell carcinoma (HNSC) is a prevalent cancer.
- Long noncoding RNAs (lncRNAs) play a role in cancer development.
- The specific function of lncRNAs in HNSC needs further investigation.
Purpose of the Study:
- To investigate the role of a novel lncRNA, HNSC-associated transcript 1 (HNSCAT1), in HNSC.
- To identify the molecular targets and regulatory mechanisms of HNSCAT1 in HNSC.
- To explore the potential of HNSCAT1 as a diagnostic or therapeutic target for HNSC.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets.
- Rapid amplification of cDNA ends (RACE) assays and RNA-FISH to validate HNSCAT1.
- High-throughput transcriptome analysis (RNA-seq) to identify HNSCAT1 targets.
- In vivo and in vitro experiments to assess HNSCAT1 function.
Main Results:
- HNSCAT1 was found to be downregulated in HNSC tumors and advanced stages.
- Overexpression of HNSCAT1 enhanced treatment efficacy in HNSC models.
- KRT80 was identified as a direct target of HNSCAT1, with a positive correlation in tumor samples.
- miR-1245 was found to interact with both HNSCAT1 and KRT80, mediating their regulatory relationship.
Conclusions:
- lncRNA HNSCAT1 acts as a tumor suppressor in HNSC.
- HNSCAT1 regulates HNSC progression through the KRT80 pathway.
- HNSCAT1 presents a novel mechanism for lncRNA function and offers potential as a diagnostic and therapeutic target for HNSC.
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