Effects of GATA6-AS/MMP9 on malignant progression of endometrial carcinoma

J BUON. 2021 Sep-Oct;26(5):1789-1795.

Abstract

Purpose: Previous studies have shown that long non-coding RNA (lncRNA) GATA6-AS is a tumor suppressor gene. However, the role of GATA6-AS in endometrial cancer (EC) has not been reported. We aimed at investigating the expression characteristics of GATA6-AS in EC tissues and cell lines, and explored whether it inhibits the malignant progression of EC through modulating matrix metalloproteinase-9 (MMP9).

Methods: GATA6-AS expression in 17 pairs of EC tissues and adjacent ones was studied by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Meanwhile, GATA6-AS expression levels in EC cell lines were also evaluated by qRT-PCR assay. In addition, GATA6-AS overexpression model was constructed using lentivirus in EC cell lines KLE and HEC-1B. The impacts of GATA6-AS overexpression model was constructed using lentivirus in EC cell lines KLE and HEC-1B on the proliferation capacity and apoptosis of EC cells were assessed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU), and flow cytometry experiments. Furthermore, we explored the interaction between GATA6-AS and MMP9 in EC cells via performing luciferase assay and cell reverse experiments.

Results: Our data showed that GATA6-AS expression in EC tissue specimens was remarkably lower than that in adjacent ones. In vitro cell experiments revealed that overexpression of GATA6-AS markedly attenuated the proliferation ability of EC cells while elevated their apoptosis. Meanwhile, luciferase assay confirmed the binding relationship between GATA6-AS and MMP9. In addition, cell reverse experiments further demonstrated the mutual regulation between GATA6-AS and MMP9, which was, overexpression of MMP9 reversed the inhibitory influence of upregulation of GATA6-AS on the malignant progression of EC.

Conclusions: lncRNA GATA6-AS, lowly expressed in EC tissue samples. Additionally, lncRNA GATA6-AS may suppress the malignant progression of EC through the modulation of regulating MMP9.

MeSH terms

  • Cell Line, Tumor
  • Disease Progression
  • Endometrial Neoplasms / genetics*
  • Female
  • GATA6 Transcription Factor / metabolism*
  • Humans
  • Transfection

Substances

  • GATA6 Transcription Factor
  • GATA6 protein, human