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Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck
Shang-Ju Tang1,2, Guo-Rong You1, Joseph T Chang3,4
1Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Abstract:
Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.
Insights
Researchers identified 31 long non-coding RNAs (lncRNAs) that are dysregulated in head and neck cancer (HNC). This lncRNA panel can predict patient prognosis and offers potential for precision medicine in HNC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Head and neck cancer (HNC) is a prevalent malignancy with incompletely understood molecular mechanisms.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in cancer, but their specific involvement in HNC requires further elucidation.
- Limited expression profiling data hinders the understanding of lncRNAs in HNC pathogenesis.
Purpose of the Study:
- To systematically identify and characterize lncRNAs associated with head and neck cancer.
- To establish a prognostic signature panel of lncRNAs for HNC patients.
- To investigate the functional role of specific lncRNAs, such as XIST, in HNC aggressiveness.
Main Methods:
- Screening of a cancer-related lncRNA profile PCR array to identify dysregulated lncRNAs in HNC cells.
- Analysis of The Cancer Genome Atlas (TCGA) database for prognostic significance of lncRNAs in HNC.
- Validation of lncRNA expression in clinical HNC samples and cell lines.
- Functional assays including gene silencing (RNAi) and pathway enrichment analyses (GO, KEGG).
Main Results:
- A total of 55 lncRNAs were found to be dysregulated in HNC cells compared to normal keratinocytes.
- Fifteen lncRNAs significantly correlated with overall survival in HNC patients from TCGA data.
- A 31-lncRNA signature panel was identified, capable of predicting HNC prognosis, with XIST, HOXA11-AS, and MALAT1 being notably dysregulated.
- Silencing of XIST reduced invasion and migration in HNC cell lines, indicating its role in cancer aggressiveness.
Conclusions:
- A 31-lncRNA panel serves as a robust prognostic signature for head and neck cancer.
- The identified lncRNAs, particularly XIST, play significant roles in HNC progression, including proliferation and metastasis.
- This study provides a foundation for utilizing these lncRNAs in precision medicine strategies for HNC.
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