Abstract
Oral submucous fibrosis (OSF) as one of the premalignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. However, the role of long non-coding RNA (lncRNA) expression in OSF malignant progression still remains poorly understood. Through RNA-sequencing normal mucous, OSF and OSCC tissues, we found 687 lncRNA transcripts significantly and differentially expressed during OSF progression, including 231 upregulated lncRNAs and 456 downregulated lncRNAs, indicating that lncRNAs are involved in the regulation of different stages of OSF development. Further functional enrichment analysis showed these differentially expressed lncRNAs participated in inflammation signaling, Wnt signaling, angiogenesis, CCKR signaling, integrin signaling, PDGF signaling, p53 signaling, and EGF receptor (EGFR) signaling pathways, which contribute to inflammatory and fibroelastic pathogenetic changes of OSF and further malignant progression. Five novel lncRNAs were differentially expressed during OSF progression with varied expression levels, indicating the importance of these lncRNAs in OSF malignant development. Moreover, some lncRNAs have been previously identified to be associated with OSCC pathogenesis, including HCG22, RP11-397A16.1, LINC00271, CTD-3179P9.1, and ZNF667-AS1. Thus, our study firstly comprehensively elucidated lncRNAs expression profile of malignant procession from OSF premalignant lesion to OSCC, which will enlighten our understanding of the importance of lncRNA involved in OSF malignant development.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumors in head and neck [1]
To comprehensively identify the long non-coding RNA (lncRNA) landscape in Oral submucous fibrosis (OSF) malignant progression, we performed lncRNA expression profile of 2 normal mucous tissues, 8 OSF tissues with different stages and 8 OSCC combined with OSF tissues using RNA sequencing
A total of ∼1.5-2.0 billion clean reads of each sample were obtained after mapped to the human reference genome using hierarchical indexing for spliced alignment of transcripts (HISAT) (Table S1; Figure 1(a)), of which more than 74% of the average reads were mapped to the human reference genome and more than 40% of the average reads were uniquely mapped to the genome (Table S2)
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumors in head and neck [1]. OSCC has the characteristics of rapid progress, wide infiltration range, easy cervical lymphatic metastasis and poor prognosis [2, 3]. OSCC patients have a lower rate of early visits (< 50%), which directly impede enhancement of 5-year survival rate. OSF can be divided into early, middle and late stages pathologically, which may be three steps during OSF developing OSCC [6]. Malignant transformation rate of OSF has been increasing with range from 3% to 19% [6, 7]. Identification of molecular markers for early detection and diagnosis of OSF malignant progression is urgent
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