c-Myc induced the regulation of long non-coding RNA RHPN1-AS1 on breast cancer cell proliferation via inhibiting P53

Mol Genet Genomics. 2019 Oct;294(5):1219-1229. doi: 10.1007/s00438-019-01572-w. Epub 2019 May 14.

Abstract

The global burden of breast cancer has been increasing, the mechanism of which is related to multifactorial accumulation of gene mutations. Dysregulation of long noncoding RNA (LncRNA) has been linked to multiple kinds of tumorigenesis. We aimed to identify functionally relevant targets of RHPN1 Antisense RNA 1 (RHPN1-AS1) in breast cancer using breast cancer cell line-based model. Quantitative RT-PCR revealed higher expression levels of RHPN1-AS1 in human breast cancer tissues and cell line MCF-7. RHPN1-AS1 was also located in MCF-7 cells by fluorescence in situ hybridization and western blot assays. Knockdown of RHPN1-AS1 delivered by lentivirus system inhibited MCF-7 cell proliferation indicated by the cell proliferation and colony formation assays, and the knockdown of RHPN1-AS1 enhanced P53 protein expression in MCF-7 and MDA-MB-231 cells. In addition, luciferase reporter assay validated that RHPN1-AS1 is a molecular sponge of miR-4261, and direct transcriptional target of c-Myc. RHPN1-AS1 exerts tumorigenesis by regulating P53 expression via MDM2 gene. These findings provide insights into the role and mechanism of action of lncRNA RHPN-AS1 in breast cancer.

Keywords: Breast cancer; Long noncoding RNA; MDM2; P53; RHPN1-AS1.

MeSH terms

  • Breast Neoplasms / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques / methods
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • MCF-7 Cells
  • MicroRNAs / genetics
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Long Noncoding / genetics*
  • Transcription, Genetic / genetics
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • long noncoding RNA RHPN1-AS1, human