Long Non-Coding RNA Expression Profile Associated with Malignant Progression of Oral Submucous Fibrosis

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.

Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling

“…Some lncRNAs are cancer specific and their expression levels have been found to be indicative of severity of the disease (Zhang et al , 2019). Dysregulation of lncRNAs is evident in OSCC (Nishiyama et al , 2018; Sur et al , 2019b; Zhang et al , 2019; Zhou et al , 2019). The TCGA dataset and other transcriptome arrays have revealed differential expression of many lncRNAs in human OSCC as compared to non‐tumor oral mucosa, and there is an association of these lncRNAs with cell proliferation, survival, migration, and genomic stability (Zhang et al , 2019; Zhou et al , 2019).…”

Oral Submucous Fibrosis: A Review on Biomarkers, Pathogenic Mechanisms, and Treatments

“…Common alterations of the epigenetic regulation are also reported in late-stage OSF and OSCC. The hypermethylation of WIF1, p16, which was mentioned in Section 1.4 , and the expression of long-noncoding RNA HCG22, RP11-397A16.1, LINC00271, CTD-3179P9.1, and ZNF667-AS1 [ 129 ] have been reported and may contribute to OSF malignant development.…”

Long non‑coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma (Review)

“…Research into lncRNAs has increased in the last 5 years; however, the function of numerous lncRNAs in OSF remains unclear. To date, only four articles have illustrated the relative issues (72)(73)(74)(75).…”

“…The lncRNA sequencing conducted in 2019 by Zhou et al (75) included 13 normal mucous samples, 10 OSF samples, and 20 OScc samples. A total of 5 dE candidate lncRNAs were found to participate in the inflammatory signaling pathway and contributed to inflammatory and fibroelastic pathogenetic changes by deregulating their cis-target and trans-target genes in OSF malignant development.…”