miR-18a expression in basal cell carcinoma and regulatory mechanism on autophagy through mTOR pathway.

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Basal cell carcinoma (BCC) is the most common form of skin carcinoma.To investigate the function of key miRNA and explore the potential molecular mechanisms involved in BCC.Microarray dataset GSE34535 (including seven BCC samples and seven control samples) was downloaded from Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were identified. We enrolled 20 patients with BCC and 20 healthy individuals as a control group, to compare the miR-18a expression in their tissue samples, also the expression of miR-18a in A431 and HaCaT cells was detected. Following this, we up-regulated and down-regulated miR-18a expression in A431 cells to examine the cell proliferation, migration and apoptosis. To further investigate the relative mechanism, the LC3, Beclin 1, Akt and mTOR were examined by Quantitative real-time PCR and Western blot. For further verification, we examined the expression of LC3 in BCC patients and control group.Nineteen common DE-miRNAs (thirteen up-regulated and six down-regulated) by BCC and control were identified. miR-18a were about 3-fold higher in BCC tissues and A431 cells compared with the control group. In vitro, down-regulation of miR-18a was shown to inhibit cell proliferation and activate autophagy via Akt/mTOR signaling pathway, while up-regulation of miR-18a promoted cell proliferation of these cells. Compared with the control group, the LC3 was decreased in BCC tissue samples.Our data support an oncogenic role of miR-18a through a novel Akt/mTOR/Beclin 1/LC3 axis and suggest that the antitumor effects of miR-18a inhibitor may make it suitable for BCC therapy.

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