LncRNA MCM3AP-AS1 promotes proliferation and invasion through regulating miR-211-5p/SPARC axis in papillary thyroid cancer

Endocrine. 2019 Aug;65(2):318-326. doi: 10.1007/s12020-019-01939-4. Epub 2019 Apr 27.

Abstract

Background: Long non-coding RNAs (lncRNAs) are an emerging class of regulators in cancer. A lncRNA, MCM3AP-AS1, has been demonstrated as a versatile mediator in many cancers, except papillary thyroid cancer. The aim of this study is to investigate the role and mechanism of MCM3AP-AS1 in papillary thyroid cancer.

Methods: Quantitative real-time PCR was used to assess the level of MCM3AP-AS1 and miR-211-5p in papillary thyroid cancer tissues and cells. Western blot was used to detect E-cadherin and secreted protein acidic and cysteine rich (SPARC) protein levels. CCK-8, scratch wound assay, and transwell assay were used to evaluate papillary thyroid cancer cell proliferation, migration, and invasion, respectively. BLAST alignment and luciferase assay were used to explore the interaction among MCM3AP-AS1, mi/r-211, and SPARC.

Results: In papillary thyroid cancer, MCM3AP-AS1 was upregulated, while miR-211 was downregulated. MCM3AP-AS1 overexpression promoted papillary thyroid cancer proliferation, migration, and invasion. Further, MCM3AP-AS1 was shown to be negatively correlated with miR-211-5p. We next validated that miR-211-5p overexpression could reverse the promoting role of MCM3AP-AS1 in papillary thyroid cancer, whereby SPARC plays an important regulating role. In vivo, we confirmed the anti-tumor role of MCM3AP-AS1 silencing and the close relation among MCM3AP-AS1, miR-211-5p, and SPARC.

Conclusions: MCM3AP-AS1 promotes papillary thyroid cancer by regulating the MCM3AP-AS1/miR-211-5p/SPARC axis, which could potentially be a therapeutic target in papillary thyroid cancer.

Keywords: MCM3AP-AS1; Papillary thyroid cancer; Therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MicroRNAs / metabolism*
  • Osteonectin / metabolism*
  • RNA, Long Noncoding / metabolism
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN211 microRNA, human
  • MicroRNAs
  • Osteonectin
  • RNA, Long Noncoding
  • SPARC protein, human
  • Acetyltransferases
  • MCM3AP protein, human