RNF185 antisense RNA 1 (RNF185-AS1) promotes proliferation, migration, and invasion in papillary thyroid carcinoma

Anticancer Drugs. 2022 Jul 1;33(6):595-606. doi: 10.1097/CAD.0000000000001295. Epub 2022 Mar 23.

Abstract

Long noncoding RNA (lncRNA) plays an important role in multiple cancers. So far, the exact function of lncRNAs in papillary thyroid carcinoma (PTC) is unclear. The purposes of this work were to investigate the function and underlying mechanisms of RNF185 antisense RNA 1 (RNF185-AS1) in PTC. The expression of RNF185-AS1 was analyzed by quantitative real-time PCR (qRT-PCR). Colony formation, 5-ethynyl-2'-deoxyuridine, and Cell Counting Kit-8 assays were utilized to determine cell proliferation. Cell migration and invasion were tested using wound healing and transwell assays. A mouse transplantation tumor model was used for tumor growth analyses in vivo. The regulation of RNF185-AS1 on the downstream miR-429/lipoprotein receptor-related protein (LRP4) axis was predicted and identified through bioinformatic analysis, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. RNF185-AS1 was dramatically overexpressed in PTC tumors and cells. High RNF185-AS1 expression was associated with bigger tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage in PTC patients. Silencing of RNF185-AS1 impeded the proliferation, migration, and invasion in vitro and constrained tumorigenesis in vivo. Mechanistically, RNF185-AS1 could act as a sponge of miR-429 to regulate the expression of LRP4. In addition, downregulation of miR-429 or upregulation of LRP4 could relieve the proliferation, migration, and invasion of IHH-4 and TPC-1 cells that inhibited by RNF185-AS1 knockdown. Downregulation of RNF185-AS1 may suppress PTC progression through functioning as a sponge of miR-429 to hinder the expression of LRP4. The RNF185-AS1/miR-429/LRP4 axis will lay the groundwork for future therapeutic strategies in PTC.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitochondrial Proteins
  • RNA, Antisense / genetics*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms* / pathology
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • MicroRNAs
  • Mitochondrial Proteins
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNF185 protein, human
  • Ubiquitin-Protein Ligases