LncRNA DANCR upregulation induced by TUFT1 promotes malignant progression in triple negative breast cancer via miR-874-3p-SOX2 axis

Exp Cell Res. 2020 Nov 15;396(2):112331. doi: 10.1016/j.yexcr.2020.112331. Epub 2020 Oct 13.

Abstract

Triple negative breast cancer (TNBC) is a subtype of breast cancer with poorest survival outcome and is prone to metastasis. TUFT1 and the long non-coding RNA (lncRNA), DANCR, play vital roles in metastasis and progression of various cancers. However, the correlation between TUFT1 and DANCR in TNBC and their downstream molecular mechanisms are still undetermined. We demonstrated that upregulation of TUFT1 in TNBC was related to a worse survival in TNBC patients. The TNBC cells invasiveness was augmented by TUFT1 in a dose-dependent manner, while inhibiting TUFT1 repressed the invasiveness. Particularly, the expression of TUFT1 was positively correlated with the expression of DANCR in TNBC tissues. In addition, TUFT1 increased DANCR expression, while silencing DANCR ameliorated the invasiveness of TNBC cells induced by TUFT1. As demonstrated, TUFT1 interacted with miR-874-3p. Subsequently, qRT-PCR together with luciferase reporter further demonstrated that DANCR acted as competing endogenous (ceRNA) for miR-874-3p, thereby regulating the de-repression of SOX2 and advancing epithelial-mesenchymal transition (EMT) in TNBC. The present research shows that TUFT1 promotes the malignant development in TNBC via enhancing the expression of DANCR. The upregulation of DANCR may contribute to the progression and tumor invasiveness of TNBC, considering that DANCR functions as a miR-874-3p sponge, thus modulating SOX2 positively. Collectively, the present study explored the molecular mechanism underlying TUFT1 in TNBC, raising a TUFT1-mediated therapy for the treatment of patients with TNBC.

Keywords: LncRNA DANCR; TUFT1; Triple negative breast cancer; ceRNA; miR-874-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Dental Enamel Proteins / metabolism*
  • Disease Progression*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • SOXB1 Transcription Factors / metabolism*
  • Survival Analysis
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation / genetics*

Substances

  • DANCR long noncoding RNA, human
  • Dental Enamel Proteins
  • MIRN874 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • tuftelin