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NCK1 antisense RNA 1 (NCK1-AS1) exerts pro-fibrosis property in oral mucosa through modulation of miR-137/NCK1 axis
Yu-Feng Huang1,2, Yu-Lei Wei1,3, Shih-Min Wang1,3
1School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Background/Purpose:
Oral submucous fibrosis (OSF) is a premalignant condition of the oral cavity, and its pathogenesis remains largely unknown. A multitude of non-coding RNAs are aberrantly expressed in OSF, and their implication for the development of OSF is a matter meriting investigation.
Materials And Methods:
The functional role of long non-coding RNA NCK1-AS1 in myofibroblast activation of fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues was assessed. Wound healing, collagen gel contraction and transwell migration assays have been employed to assess the myofibroblast activities. In addition, a luciferase-based reporter assay was used to illustrate the potential mechanism underlying the regulation of NCK1-AS1 in myofibroblast activation.
Results:
Silencing of NCK1-AS1 markedly downregulated myofibroblast activation and the expression of fibrosis markers in fBMFs. Besides, we demonstrated that NCK1-AS1 directly interacted with microRNA-137 (miR-137) and was negatively correlated with it. Moreover, we found that NCK1 was a target of miR-137 and positively related to NCK1-AS1. Our results demonstrated that NCK1-AS1 may regulate myofibroblast activation by suppressing miR-137 and upregulating NCK1.
Conclusion:
We showed that NCK1-AS1 acted as a sponge of miR-137 and titrated the suppressive effect of miR-137 on NCK1 to modulate myofibroblast activation in OSF condition.
Insights
Long non-coding RNA NCK1-AS1 promotes oral submucous fibrosis (OSF) by acting as a sponge for microRNA-137 (miR-137), upregulating NCK1 and myofibroblast activation in this premalignant condition.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Oral submucous fibrosis (OSF) is a premalignant oral condition with unknown pathogenesis.
- Aberrant expression of non-coding RNAs is observed in OSF, suggesting their role in disease development.
Purpose of the Study:
- To investigate the functional role of long non-coding RNA NCK1-AS1 in myofibroblast activation in OSF.
- To elucidate the molecular mechanism by which NCK1-AS1 influences fibrotic buccal mucosal fibroblasts (fBMFs).
Main Methods:
- Assessed myofibroblast activities using wound healing, collagen gel contraction, and transwell migration assays.
- Utilized a luciferase-based reporter assay to determine the regulatory mechanism of NCK1-AS1.
Main Results:
- Silencing NCK1-AS1 reduced myofibroblast activation and fibrosis markers in fBMFs.
- NCK1-AS1 directly interacted with and suppressed microRNA-137 (miR-137).
- NCK1 was identified as a target of miR-137, with NCK1-AS1 positively correlating with NCK1 expression.
Conclusions:
- NCK1-AS1 acts as a molecular sponge for miR-137, inhibiting its suppressive effect on NCK1.
- This mechanism modulates myofibroblast activation in the context of oral submucous fibrosis.
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