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Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway
Quan Luo1, Wei Li1, Tian Zhao1
1Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, China.
Abstract:
Dysregulation of miRNAs is a common feature in human cancers, but there are lack of studies on roles of miRNAs in cutaneous squamous cell carcinoma (CSCC). miR-148a, a member of the miR-148/152 family, has been found to be downregulated in different types of cancer and its role in CSCC remains unknown. The study was aimed to investigate the expression and cellular function of miR-148a in CSCC. We found that miR-148a was underexpressed in CSCC tissues and cell lines. MAP3K2, MAP3K4 and MAP3K9 were predicted as the target genes of miR-148a and the latter two genes were verified as the target genes of miR-148a in CSCC cells. Importantly, we demonstrated that the overexpression of miR-148a significantly inhibited CSCC cell proliferation and metastasis via down-regulation of MAP3K9 and MAP3K4 expression. MAP3K4 and MAP3K9 were negatively associated with the expression of miR-148a in CSCC tissues. Our results suggested indicated that miR-148a acts as a tumor suppressor of CSCC via inhibiting MAPK pathway. These results may provide a promising alterative strategy for CSCC therapy.
Insights
MicroRNA-148a (miR-148a) is downregulated in cutaneous squamous cell carcinoma (CSCC). Overexpressing miR-148a inhibits CSCC cell proliferation and metastasis by targeting MAP3K4 and MAP3K9, suggesting its tumor-suppressive role.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA (miRNA) dysregulation is common in human cancers.
- The role of miR-148a in cutaneous squamous cell carcinoma (CSCC) is largely unknown.
- miR-148a is frequently downregulated in various cancer types.
Purpose of the Study:
- To investigate the expression and cellular function of miR-148a in CSCC.
- To identify target genes of miR-148a in CSCC.
- To explore the therapeutic potential of miR-148a in CSCC.
Main Methods:
- Quantitative real-time PCR to assess miR-148a expression in CSCC tissues and cell lines.
- Bioinformatic prediction and experimental validation of miR-148a target genes (MAP3K2, MAP3K4, MAP3K9).
- In vitro assays to evaluate the effect of miR-148a overexpression on CSCC cell proliferation and metastasis.
Main Results:
- miR-148a was significantly underexpressed in CSCC tissues and cell lines.
- MAP3K4 and MAP3K9 were validated as direct targets of miR-148a in CSCC.
- Overexpression of miR-148a inhibited CSCC cell proliferation and metastasis by downregulating MAP3K4 and MAP3K9.
- MAP3K4 and MAP3K9 expression were negatively correlated with miR-148a levels in CSCC tissues.
Conclusions:
- miR-148a functions as a tumor suppressor in CSCC.
- The tumor-suppressive activity of miR-148a is mediated through the inhibition of the MAPK pathway via MAP3K4 and MAP3K9.
- miR-148a represents a potential therapeutic target for CSCC treatment.
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