Hsa_circRNA_102229 facilitates the progression of triple-negative breast cancer via regulating the miR-152-3p/PFTK1 pathway

J Gene Med. 2021 Sep;23(9):e3365. doi: 10.1002/jgm.3365. Epub 2021 Jun 16.

Abstract

Background: Increasing evidence has suggested that circular RNAs (circRNAs) may act as an important regulatory factor in tumor progression. However, how circRNAs exert their functions in triple-negative breast cancer (TNBC) remains not clearly understood.

Methods: First, circRNA microarrays were conducted to identify aberrantly expressed circRNAs in TNBC tissues. Kaplan-Meier survival analysis was conducted to calculate the correlation between the level of hsa_circRNA_102229 and outcomes of patients with TNBC. The effect of hsa_circRNA_102229 and serine/threonine-protein kinase PFTAIRE 1 (PFTK1) on TNBC cells was clarified by cell counting kit-8, transwell and wound healing assays, as well as by a flow cytometry. The molecular mechanism of hsa_circRNA_102229 was clarified through bioinformatics, a dual-luciferase reporter assay, western blotting, fluorescence in situ hybridization and real-time polymerase chain reaction. Tumor xenograft experiments were performed to analyze growth and metastasis of TNBC in vivo.

Results: In TNBC tissues and cells, hsa_circ_102229 was remarkably up-regulated. Patients with TNBC presenting high hsa_circ_102229 exhibited poor prognosis. Moreover, hsa_circ_102229 could promote the migration, proliferation and invasion, whereas it inhibited the apoptosis of TNBC cells. Furthermore, hsa_circ_102229 directly targeted miR-152-3p and could regulate the expression of PFTK1 by targeting miR-152-3p. Rescue assays suggested that hsa_circ_102229 may exert its function in TNBC cells by regulating PFTK1. Additionally, knockdown of hsa_circ_102229 slowed down TNBC tumorigenesis and lung metastasis in a tumor xenograft animal model.

Conclusions: Hsa_circ_102229 might serve as a competing endogenous RNA (ceRNA) to modulate PFTK1 expression via regulating miR-152-3p to affect the functions of TNBC cells. Hsa_circ_102229 acts as a newly discovered biomarker for TNBC treatment.

Keywords: PFTK1; hsa_circRNA_102229; miR-152-3p; prognosis; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Animals
  • Apoptosis
  • Biomarkers
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin-Dependent Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Prognosis
  • RNA, Circular / physiology*
  • Signal Transduction
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers
  • MIRN152 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • CDK14 protein, human
  • Cyclin-Dependent Kinases