Upregulated IncRNA WTAPP1 in Triple Negative Breast Cancer Predicts Survival

Crit Rev Eukaryot Gene Expr. 2022;32(1):67-78. doi: 10.1615/CritRevEukaryotGeneExpr.2021039983.

Abstract

The migration and angiogenesis of endothelial progenitor cells require the involvement of WTAPP1. Cell migration and angiogenesis are critical for cancer development, we therefore speculated that WTAPP1 may participate in cancer biology. This study aimed to explore the role of WTAPP1 in triple-negative breast cancer (TNBC). A total of 68 patients (females, 38 to 67 years old, mean age 52.1 ± 5.9 years old) were enrolled in this study. The effects of over-expression of WTAPP1 and miR-34a on EEF2K were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Transient cell transfections were performed to explore the interactions between genes. Cell proliferation assay was used to analyze cell proliferation. Transwell assays were performed to detect cell invasive and migration. Flow cytometry was used to evaluate apoptosis. WTAPP1 was upregulated in tumor tissues of TNBC patients and high expression levels of WTAPP1 in tumor tissues predicted poor survival. In contrast, miR-34a was downregulated in TNBC. Correlation analysis showed that WTAPP1 and miR-34a were negatively correlated with each other. In cancer cells, overexpression of WTAPP1 resulted in downregulation of miR-34a. Remarkably, overexpression of WTAPP1 increased the expression levels of EEF2K, a target of miR-34a. Overexpression of WTAPP1 and EEF2K increased proliferation, invasion and migration of TNBC cells, while overexpression of miR-34a showed different results. In addition, overexpression of miR-34a enhanced the effects of overexpression of WTAPP1 and EEF2K on apoptosis. WTAPP1 may promote TNBC cell proliferation by downregulating miR-34a.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • MicroRNAs