Exosome‐derived long non‐coding RNA ADAMTS9‐AS2 suppresses progression of oral submucous fibrosis via AKT signalling pathway

Oral submucosal fibrosis (OSF) is a precancerous condition in the oral cavity and areca nut consumption has been regarded as one of the etiologic factors implicated in the development of OSF via persistent activation of buccal mucosal fibroblasts (BMFs). It has been previously reported that an epithelial to mesenchymal transition (EMT) factor, ZEB1, mediated the areca nut-associated myofibroblast transdifferentiation. In the current study, we aimed to elucidate how areca nut affected non-coding RNAs and the subsequent myofibroblast activation via ZEB1. We found that long non-coding RNA LINC00084 was elicited in the BMFs treated with arecoline, a major alkaloid of areca nut, and silencing LINC00084 prevented the arecoline-induced activities (such as collagen gel contraction, migration, and wound healing capacities). The upregulation of LINC00084 was also observed in the OSF tissues and fibrotic BMFs (fBMFs), and positively correlated with several fibrosis factors. Moreover, we showed knockdown of LINC00084 markedly suppressed the myofibroblast features in fBMFs, including myofibroblast phenotypes and marker expression. The results from the luciferase reporter assay confirmed that LINC00084 acted as a sponge of miR-204 and miR-204 inhibited ZEB1 by directly interacting with it. Altogether, these findings suggested that the constant irritation of arecoline may result in upregulation of LINC00084 in BMFs, which increased the ZEB1 expression by sequestering miR-204 to induce myofibroblast transdifferentiation.

Download Full-text

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

Journal of Oncology ◽

10.1155/2019/6835176 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Shanghui Zhou ◽

Yun Zhu ◽

Zhijing He ◽

Dahe Zhang ◽

Feng Guo ◽

...

Keyword(s):

Expression Profile ◽

Egf Receptor ◽

Oral Submucous Fibrosis ◽

Enrichment Analysis ◽

Malignant Progression ◽

Functional Enrichment ◽

Differentially Expressed ◽

Non Coding Rna ◽

Submucous Fibrosis ◽

Long Non Coding Rna

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.

Download Full-text