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

Abstract

Summary Background Basal cell carcinoma (BCC) is the most common form of skin carcinoma. Aim To investigate the function of key micro(mi)RNAs and to explore the potential molecular mechanisms involved in BCC. Methods The microarray dataset http://GSE34535, which comprises seven BCC samples and seven control samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE‐miRNAs) were identified. We collected tissue samples from 20 patients with BCC and 20 healthy controls (HCs), to compare the miR‐18a expression in their tissue samples. Expression of miR‐18a in A431 and HaCaT cells was also assayed. Following this, we upregulated and downregulated miR‐18a expression in A431 cells to examine the effects on cell proliferation, migration and apoptosis. To further investigate the relative mechanism, the proteins LC3, Beclin 1, Akt and mammalian target of rapamycin (mTOR) were examined by quantitative real‐time PCR and Western blotting. For further verification, we examined the expression of LC3 in the 20 BCC and 20 HC tissue samples. Results In total, 19 DE‐miRNAs (13 upregulated and 6 downregulated) that were common to the BCC and HC groups were identified. Levels of miR‐18a were about three‐fold higher in BCC tissues and A431 cells compared with their respective control groups. In vitro, downregulation of miR‐18a was shown to inhibit cell proliferation and activate autophagy via the Akt/mTOR signalling pathway, while upregulation of miR‐18a promoted proliferation of these cells. LC3 was decreased in BCC compared with HC tissue samples. Conclusions Our data support an oncogenic role of miR‐18a through a novel Akt/mTOR/Beclin 1/LC3 axis, and suggest that the antitumour effects of miR‐18a inhibitor may make it suitable for BCC therapy.

Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review

“…Lastly, the in vitro downregulation of microRNA-18a (miR-18a), a differentially elevated miRNA in basal cell carcinoma, was found to inhibit cell proliferation and activate autophagy through the Akt/mTOR signaling pathway. Conversely, miR-18a upregulation, characteristic of basal cell carcinoma, promoted cellular proliferation [ 65 ]. These studies demonstrate ncRNA dysregulation in basal cell carcinoma and highlight potential mechanisms in which ncRNA may regulate and promote carcinogenesis.…”

Non-coding RNAs in skin cancers:Biological roles and molecular mechanisms

“…MiR-451a inhibits BCC cell growth and colony formation by targeting TBX1, which may serve as an effective therapeutic target for BCC ( Sun and Jiang 2018 ). MiR-18a expression is significantly increased in BCC tissues and cells and promotes BCC malignant progression by targeting the Akt/mTOR/Beclin 1/LC3 axis ( Mi et al, 2020 ). MiR-17-92 cluster members and miR-143–145 cluster members are involved in BCC progression as pro-oncogenes and oncogenes, respectively ( Sand et al, 2017 ).…”