Oncogenic potential of TSTA3 in breast cancer and its regulation by the tumor suppressors miR-125a-5p and miR-125b

Tumour Biol. 2016 Apr;37(4):4963-72. doi: 10.1007/s13277-015-4178-4. Epub 2015 Nov 3.

Abstract

TSTA3 participates in enzyme metabolism and affects glycosylation processes, and abnormal glycosylation influences the malignant transformation of cells and tumor development. However, studies have not examined the molecular biological function of TSTA3 in breast cancer (BC). The expression of TSTA3 was examined in BC tissues and cell lines. Kaplan-Meier survival tests and Cox regression were used to analyze prognosis. TSTA3 depletion was used to analyze cell function. The upstream miRNAs of TSTA3 were predicted, and the downstream target gene was analyzed using a RT2 Profiler™ PCR array. Our results show that TSTA3 was highly expressed in BC tissues and cells and was correlated with poor survival. The expression of TSTA3 was correlated with the TNM status (P < 0.01) and served as an independent prognostic factor (P = 0.041). TSTA3-siRNA decreased cell invasion and proliferation in vitro. miR-125a-5p and miR-125b are upstream targets of TSTA3, and a PCR array revealed that TSTA3 affects the CXCR4-CXCL12 genes. The findings suggest that miR-125a-5p/miR-125b suppress the expression of TSTA3, which controls cell proliferation and invasion by regulating CXCR4 expression. In conclusion, a high expression of TSTA3 exerts a proto-oncogenic effect during carcinogenesis and serves as an independent molecular marker for BC patients.

Keywords: Breast cancer; Invasion; Proliferation; TSTA3; miR-125a-5p; miR-125b.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carbohydrate Epimerases / biosynthesis*
  • Carbohydrate Epimerases / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Kaplan-Meier Estimate
  • Ketone Oxidoreductases / biosynthesis*
  • Ketone Oxidoreductases / genetics
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • RNA, Small Interfering

Substances

  • Biomarkers, Tumor
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • TSTA3 protein, human
  • Ketone Oxidoreductases
  • Carbohydrate Epimerases