J Endocrinol Invest. 2022 Jan;45(1):17-28. doi: 10.1007/s40618-021-01606-4. Epub 2021 Jun 18.

microRNA-181a promotes the oncogene S100A2 and enhances papillary thyroid carcinoma growth by mediating the expression of histone demethylase KDM5C

Y Wang  1 H Ye  2 Y Yang  3 J Li  4 A Cen  4 L Zhao  3 Affiliations

Abstract

Background and purpose: Papillary thyroid carcinoma (PTC) is an endocrine malignancy. Increasing evidence highlights microRNAs (miRNAs) as important participants in PTC. Here, we investigated the role of miR-181a in PTC.

Methods: A microarray-based analysis was performed to identify the differential expression of miR-181a in PTC, which was validated with RT-qPCR. Protein expression of the proliferation-related factor Ki-67 and apoptosis- and migration-related factors in PTC was assessed with immunoblot analysis. A dual-luciferase reporter gene assay was adopted to verify the relationship between miR-181a and lysine demethylase 5C (KDM5C). Chromatin immunoprecipitation (ChIP) was used to detect the level of the H3K4me3 modification on S100 calcium-binding protein A2 (S100A2). Cell viability, apoptosis, and invasion and migration abilities were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. The in vitro results were verified in in vivo nude mouse models.

Results: miR-181a was highly expressed in PTC tissues and cell lines. Silencing miR-181a repressed the proliferation and migration of PTC cells. KDM5C was identified as the target gene of miR-181a and represses S100A2 expression through histone demethylation to diminish the migration and proliferation of PTC cells. miR-181a depletion suppressed tumor growth.

Conclusion: Collectively, these results suggest that highly expressed miR-181a promotes the proliferation of PTC cells by increasing the expression of the oncogene S100A2. This study contributes to the advancement of miR-181a-targeted therapeutics.

Keywords: Cell proliferation; Lysine demethylase 5C; Papillary thyroid carcinoma; S100 calcium-binding protein A2; microRNA-181a.

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