The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma

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.

A cuproptosis-related lncRNA signature predicts the prognosis and immune cell status in head and neck squamous cell carcinoma

“…In the lncRNAs above, EIF3J-DT, PDCD4-AS1, CDKN2A-DT, MIR9-3HG, LINC01269, and EMSLR have been reported to play a critical role in the regulation of cancers ( 24 – 29 ). In particular, a previous study revealed that LINC01269 could be a tumor inhibitor as it triggered therapeutic efficacy in HNSCC ( 28 ), which validated the analysis result that LINC01269 was significantly correlated with the progression of HNSCC tumor grade in the current study. These results fully demonstrated that CRLs have potential effects on the initiation and progression of HNSCC in clinical applications and can be used to construct the progression or prognosis prediction model.…”

The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer

“…KRT80 expression promoted proliferation, migration, invasion and EMT of colorectal cancer cells by interacting with PRKDC via Akt pathway. 5 Zhao et al 15 demonstrated that NSCAT1 competed with miR-1245 to suppress the inhibitory effects of miR-1245 on the translation of KRT80 in head and neck squamous cancer cells. KRT80 knockdown reduced the viability and of colorectal cells.…”

COADREADx: A comprehensive algorithmic dissection unravels salient biomarkers and actionable insights into the discrete progression of colorectal cancer

“…There is emerging evidence for the role of KRT80 in head and neck squamous cell carcinoma (Zhao et al, 2022), but it is not a known cancer driver (https://www.intogen.org/search?gene=KRT80). The gene OTOP2 has been identified as a TSG, as it was significantly downregulated in the cancer phenotype.…”