MicroRNA-200c-3p Negatively Regulates ATP2A2 and Promotes the Progression of Papillary Thyroid Carcinoma

Biochem Genet. 2022 Oct;60(5):1676-1694. doi: 10.1007/s10528-022-10184-w. Epub 2022 Jan 25.

Abstract

microRNA-200c-3p (miR-200c-3p) has emerged as an important tumor growth regulator. However, its function in papillary thyroid carcinoma (PTC) is poorly understood. This study was conducted to investigate the role of miR-200c-3p in the progression of human PTC. The miR-200c-3p expression in human PTC tissues and cell lines was evaluated. The target relationship between miR-200c-3p and candidate genes was predicted through bioinformatic analysis and confirmed with a luciferase reporter assay. miRNA or gene expression was altered using transfection, and cell behavior was analyzed using CCK-8, wound healing, Transwell, and colony formation assays. The tumor-promoting effects of miR-200c-3p were evaluated by xenografting tumors with K1 cells in nude mice. The expression level of miR-200c-3p in human PTC tissues and cell lines markedly increased, and this increased expression was significantly associated with a worse overall survival. When inactivated, miR-200c-3p suppressed K1 cells' malignant behaviors, including decreasing proliferation and attenuating colony formation, migration, and invasion. Its inactivation also attenuated the development of xenografted K1 cells in nude mice. The effects of miR-200c-3p mimics on promoting the malignant behaviors of PTC cells were remarkably reversed by the overexpression of ATP2A2, as a downstream target of miR-200c-3p. miR-200c-3p acts as an oncogenic gene and promotes the malignant biological behaviors of human PTC cells, thereby directly targeting ATP2A2. This regulated axis may be used as a potential therapy of PTC.

Keywords: ATP2A2; Metastasis; Papillary thyroid carcinoma; Proliferation; miR-200c-3p; microRNA.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases* / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases* / metabolism
  • Thyroid Cancer, Papillary* / genetics
  • Thyroid Cancer, Papillary* / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • ATP2A2 protein, human