lncRNA MSC-AS1 activates Wnt/β-catenin signaling pathway to modulate cell proliferation and migration in kidney renal clear cell carcinoma via miR-3924/WNT5A

J Cell Biochem. 2020 Oct;121(10):4085-4093. doi: 10.1002/jcb.29594. Epub 2020 Jan 9.

Abstract

Kidney renal clear cell carcinoma (KIRC) is the most general subtype of renal cell carcinoma, which composes about 1/20 of adult malignancies. The anomaly of long noncoding RNAs (lncRNAs) expression is proved to mediate cancer progression of various types. The function and mediation mechanism of MSC-AS1 has rarely been detected in KIRC before. This study started with the mediation of MSC-AS1 on cell function. In this study, MSC-AS1 was dramatically upregulated in KIRC and correlated with dismal prognosis of KIRC patients. Knockdown of MSC-AS1 would suppress the proliferative and migratory properties of KIRC cells. MSC-AS1 was found to directly downregulate miR-3924 expression while miR-3924 directly downregulated WNT5A expression. Meanwhile, MSC-AS1 could promote the expression of WNT5A, indicating the existence of MSC-AS1/miR-3924/WNT5A. Further assays indicated that MSC-AS1 could enhance Wnt/β-catenin pathway. By means of rescue assays, the mediation of MSC-AS1/miR-3924/WNT5A/β-catenin axis on KIRC cell proliferation, migration and migration was verified. This study revealed that MSC-AS1 regulates KIRC cell proliferation and migration via miR-3924/WNT5A/β-catenin axis. MSC-AS1 might contribute to new strategies for KIRC treatment.

Keywords: KIRC; MCF-AS1; WNT5A; miR-3924.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transfection
  • Tumor Burden / genetics
  • Wnt Signaling Pathway / genetics*
  • Wnt-5a Protein / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CTNNB1 protein, human
  • MSC protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • WNT5A protein, human
  • Wnt-5a Protein
  • beta Catenin