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

  • J Dermatol Sci. 2022 Jan;105(1):18-26. doi: 10.1016/j.jdermsci.2021.11.005.
Xiangzhi Li  1 ,  Yawen Yuan  2 ,  Yimeng Wang  2 ,  Kaisheng Xie  3 ,  Sheng Lu  4 ,  Fuqiang Chen  2 ,  Meijuan Zhou  5 ,  Peilin Zhen  6
Affiliations
  • 1. Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 2. Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 3. Department of Pathology, The Second Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, China.
  • 4. The First School of Clinical Medicine, Southern Medical University, Guangdong, China.
  • 5. Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
  • 6. Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China. Electronic address: [email protected].
PMID: 34930675 DOI: 10.1016/j.jdermsci.2021.11.005
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.

Keywords
Cutaneous squamous cell carcinoma; Flotillin2; Metastasis; MicroRNA-486–3p; Proliferation.
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