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The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.

Abstract
Papillary thyroid carcinoma (PTC), a common thyroid cancer (TC) subtype, rapidly increases in occurrence. MicroRNAs (miRNAs), which are non-coding small RNAs, have been demonstrated to play a role in cancer pathogenic mechanisms. Although miR-143 is involved in suppressing certain malignant tumor progression, its biological role is unknown in PTC. The present study found that miR-143 levels were strongly lower in PTC patient samples and cell lines, implying that miR-143 may play a biological role in PTC. Down-regulation of miR-143 resulted in the increased expression of HMGA2. Furthermore, HMGA2 was found to be a direct target of miR-143. A dual-luciferase assay confirmed a direct binding site for miR-143 was confirmed on HMGA2 using a dual-luciferase assay. Next, over-expression of miR-143 suppressed PTC cell growth as analyzed by MTT, clone formation, and Ki-67 immunofluorescence staining assays. miR-143 mimics transfection downregulated the expression of PCNA, CDK4, CDK1, and Cyclin E1. In addition, wound healing and trans-well assays revealed that miR-143 up-regulation inhibited PTC cells invasion and migration. Co-transfection of HMGA2 expression vector restored HMGA2 expression and rescued PTC cells proliferation capability in miR-143 mimics transfected PTC cells, indicating that miR-143 inhibited PTC cells proliferation via HMGA2. These observations were also obtained in xenografts experiments in nude mice. Altogether, our study shed light on miR-143's anti-cancer biological functions in PTC progression through targeting HMGA2, suggesting that restoration of miR-143 could be a potential therapeutic approach for PTC treatment.
AuthorsChao Ding, Tiefeng Shi, Gang Wu, Jianting Man, Hongyu Han, Yunfu Cui
JournalBioengineered (Bioengineered) Vol. 13 Issue 3 Pg. 6629-6640 (03 2022) ISSN: 2165-5987 [Electronic] United States
PMID35213273 (Publication Type: Journal Article)
Chemical References
  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN143 microRNA, human
  • MicroRNAs
Topics
  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • HMGA2 Protein (genetics, metabolism)
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs (genetics, metabolism)
  • Middle Aged
  • Thyroid Cancer, Papillary (genetics, metabolism, pathology)
  • Thyroid Gland (pathology)
  • Thyroid Neoplasms (genetics, metabolism, pathology)

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