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

ABSTRACT

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 miR-486-3p and FLOT2 by fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR (qRT-PCR), 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.