A Novel lncRNA HOXC-AS3 Acts as a miR-3922-5p Sponge to Promote Breast Cancer Metastasis

Cancer Invest. 2020 Jan;38(1):1-12. doi: 10.1080/07357907.2019.1695816. Epub 2019 Dec 4.

Abstract

Purpose: The function of long noncoding RNAs (lncRNA) in breast cancer metastasis remains largely unknown. In this work, the role of HOXC-AS3 in breast cancer progression was investigated.Methods: By using Cancer Genome Atlas (TCGA) Database, we investigated the expression of HOXC-AS3 in breast cancer and explored the association between HOXC-AS3 expression and prognosis. Then, we studied the biological function of HOXC-AS3 in cell migration and invasion both in vitro and in vivo. Furthermore, the target miRNA of HOXC-AS3, and the target mRNA of miR-3922-5p were proved.Results: HOXC-AS3 is aberrantly overexpressed in breast cancers especially the HER2+ type. Moreover, high expression of HOXC-AS3 has a relationship with poor clinical outcomes of breast cancer. In addition, HOXC-AS3 regulates cell Invasion and migration both in vitro and in vivo. Our results demonstrated that miR-3922-5p was a direct target of HOXC-AS3, and PPP1R1A was a target of miR-3922-5p in breast cancer.Conclusions: The novel lncRNA HOXC-AS3 acts as a miR-3922-5p sponge to upregulate PPP1R1A protein expression, and thus results in promoting breast cancer metastasis. HOXC-AS3 could be a novel therapeutic target for breast cancer therapeutics.

Keywords: HOXC-AS3; PPP1R1A; breast cancer; metastasis; miR-3922-5p.

MeSH terms

  • Animals
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Datasets as Topic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Prognosis
  • Protein Phosphatase 1 / genetics*
  • RNA, Long Noncoding / metabolism*
  • Survival Analysis
  • Time Factors
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Protein Phosphatase 1