Transcriptome sequencing uncovers novel long noncoding and small nucleolar RNAs dysregulated in head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma persists as one of the most common and deadly malignancies, with early detection and effective treatment still posing formidable challenges. To expand our currently sparse knowledge of the noncoding alterations involved in the disease and identify potential biomarkers and therapeutic targets, we globally profiled the dysregulation of small nucleolar and long noncoding RNAs in head and neck tumors. Using next-generation RNA-sequencing data from 40 pairs of tumor and matched normal tissues, we found 2808 long noncoding RNA (lncRNA) transcripts significantly differentially expressed by a fold change magnitude ≥2. Meanwhile, RNA-sequencing analysis of 31 tumor-normal pairs yielded 33 significantly dysregulated small nucleolar RNAs (snoRNA). In particular, we identified two dramatically downregulated lncRNAs and one down-regulated snoRNA whose expression levels correlated significantly with overall patient survival, suggesting their functional significance and clinical relevance in head and neck cancer pathogenesis. We confirmed the dysregulation of these noncoding RNAs in head and neck cancer cell lines derived from different anatomic sites, and determined that ectopic expression of the two lncRNAs inhibited key EMT and stem cell genes and reduced cellular proliferation and migration. As a whole, noncoding RNAs are pervasively dysregulated in head and squamous cell carcinoma. The precise molecular roles of the three transcripts identified warrants further characterization, but our data suggest that they are likely to play substantial roles in head and neck cancer pathogenesis and are significantly associated with patient survival.

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review

“…DE of HOTAIR has been assessed in six independent studies analysing 323 patients with results supporting its overexpression (Arunkumar, Deva Magendhra Rao et al., ; Fang et al., ; Lu et al., ; Wu & Xie, ; Wu et al., ; Zou et al., ). Conversely, the only study that examined HOTAIR expression in dysplastic lesions did not find significant DE (Gibb et al., ).…”

“…Non‐significant DE was found in a study examining 60 OSCCs compared to a limited number of controls (eight cases) (Arunkumar, Deva Magendhra Rao et al., ). Of interest, a study addressing the TCGA data set identified a significant underexpression in OSCC but not in TSCC (Zou et al., ).…”

“…Finally, none of the aforementioned lncRNAs were determined to be dysregulated in laryngeal SCC (Zou et al., ). Similarly, Arunkumar et al.…”

Overexpression long non-coding RNA LINC00673 is associated with poor prognosis and promotes invasion and metastasis in tongue squamous cell carcinoma

“…Furthermore, recent studies have identified multiple functional effects of lncRNAs involving in various cellular processes, such as tumor initiation, progression and metastasis, and the dysregulation of lncRNAs are a primary feature of some human cancers [16–19]. At the same time, a great quantity identified results revealed that lncRNAs play an important role in pathogenesis of head and neck cancers [20–22]. However, the TSCC associated lncRNAs and their influence on TSCC cellular progress need to be elucidated further.…”

Identification of lncRNA functions in lung cancer based on associated protein-protein interaction modules

“…For example, FAM3D-AS1 is involved in the migration and cell proliferation in head and neck squamous cell carcinoma31, but our inferred functions in basal LUSC are RNA splicing and peptidyl-amino acid modification (Table S1). The inconsistency might be due to the difference in cancer cell types since lncRNAs may play different roles in different cell lines, tissues and cancers.…”