MicroRNA-486-3p promotes the proliferation and metastasis of cutaneous squamous cell carcinoma by suppressing flotillin-2

Background: Dysregulation of miR-486-3p was related to the growth and development of a variety of cancers, but the specific function of miR-486-3p in cutaneous squamous cell carcinoma (cSCC) is not to be confirmed yet. Objective: Our present study aimed to validate the potential molecular mechanisms of miR-486-3p in cSCC and the potential of miR-486-3p as a novel target for future treatment. Methods: Human cSCC samples and normal skin tissues were applied to determine the expression level of miR486-3p and FLOT2 by fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR (qRTPCR), respectively. As well as BALB/C nude mouse tumor model, three cSCC cells lines including HSC-1, HSC-5 and A431 were utilized to demonstrate the potential function of miR-486-3p and FLOT2 in tumorigenesis. Results: Our experimental results showed that miR-486-3p was highly expressed both in tumor samples and cell lines of cSCC. Upregulation of miR-486-3p enhanced the proliferation and migration ability of cSCC cell lines and promoted tumorigenicity in vivo. Furthermore, we confirmed that FLOT2 was a direct targeted gene of miR-486-3p. In contrary to the expression level of miR-486-3p, FLOT2 was low expressed in cSCC patient specimens and cell lines. Knockdown of FLOT2 promoted tumorigenesis of cSCC; whereas FLOT2 reversed the tumor-promoting effect of miR-486-3p. Conclusion: Our data exhibited that miR-486-3p exerted its effects on carcinogenesis as an oncogene in cSCC via suppression of FLOT2. This discovery will develop new therapeutic targets of cSCC. (c) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.