LINC01433/miR-2116-3p/MYC Feedback Loop Promotes Cell Proliferation, Migration, and the Epithelial-Mesenchymal Transition in Breast Cancer

Cancer Biother Radiopharm. 2019 Aug;34(6):388-397. doi: 10.1089/cbr.2019.2772. Epub 2019 Apr 2.

Abstract

Background: It is reported that long noncoding RNAs play an important role in human cancers, including breast cancer (BC). However, the effect of long intergenic non-protein coding RNA 1433 (LINC01433) on BC development remains elusive. Materials and Methods: The expression level of LINC01433 in BC cells and a normal breast epithelial cell (MCF-10A) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). A series of functional assays was applied to measure the bio-function of LINC01433 in BC. Bioinformatics analysis and mechanistic assays were utilized to disclose the underlying mechanism involved in the LINC01433-mediated BC cellular process. Results: qRT-PCR revealed that LINC01433 was highly expressed in BC cells. In function, LINC01433 depletion suppressed BC cell proliferation, migration, and epithelial-mesenchymal transition, but induced cell apoptosis. Mechanically, chromatin immunoprecipitation and luciferase reporter assays suggested that LINC01433 was activated by its upstream transcription factor MYC proto-oncogene (MYC). The interaction between LINC01433 and miR-2116-3p was verified in BC. Additionally, MYC was validated as a target gene of miR-2116-3p. Rescue assays demonstrated that LINC01433 promoted BC cellular process via regulating miR-2116-3p/MYC axis. Conclusion: Our findings revealed a novel positive feedback loop (LINC01433/miR-2116-3p/MYC) in BC progression and discovered the novel functional genes in this BC cellular process.

Keywords: LINC01433; MYC; breast cancer; miR-2116-3p.

MeSH terms

  • Apoptosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured

Substances

  • MAS1 protein, human
  • MIRN2116 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding