Long non-coding RNA CCAT1 regulates the biological behavior of osteosarcoma cells through the miR-454-3p/ZEB2 axis

T Su1, S-D Zhang, J Zhao

  • 1Pediatric Surgery, Jining No. 1 People's Hospital, Jining, P.R. China. zhaojuan@126.com.

Abstract

Insights

Long non-coding RNA CCAT1 is upregulated in osteosarcoma (OS) and serves as a diagnostic and prognostic marker. CCAT1 promotes OS progression by targeting the miR-454-3p/ZEB2 axis, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone malignancy with significant mortality.
  • Long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression.
  • CCAT1 has emerged as a potential oncogenic lncRNA in various cancers.

Purpose of the Study:

  • To investigate the clinical utility of lncRNA CCAT1 as a diagnostic and prognostic biomarker in osteosarcoma.
  • To elucidate the underlying molecular mechanism of CCAT1 in regulating osteosarcoma cell behavior.
  • To explore CCAT1 as a potential therapeutic target for osteosarcoma.

Main Methods:

  • Serum and tumor tissue samples from 84 osteosarcoma patients and healthy controls were analyzed for CCAT1 expression.
  • In vitro experiments involved transfecting osteosarcoma cells with CCAT1 overexpression and inhibition vectors.
  • Cell proliferation, invasion, and apoptosis were assessed using CCK-8, Transwell, and flow cytometry assays.
  • Dual-luciferase reporter assays and rescue experiments were performed to determine the regulatory axis involving CCAT1, miR-454-3p, and ZEB2.

Main Results:

  • CCAT1 was significantly upregulated in osteosarcoma tissues and serum compared to controls.
  • Serum CCAT1 demonstrated high diagnostic value for osteosarcoma (AUC = 0.930).
  • High CCAT1 expression correlated with poor patient survival.
  • Inhibition of CCAT1 suppressed osteosarcoma cell proliferation and invasion while promoting apoptosis.
  • CCAT1 was found to target miR-454-3p, which in turn targets ZEB2, forming the miR-454-3p/ZEB2 axis.

Conclusions:

  • lncRNA CCAT1 is a valuable diagnostic and prognostic biomarker for osteosarcoma.
  • CCAT1 promotes osteosarcoma cell proliferation and invasion by regulating the miR-454-3p/ZEB2 axis.
  • CCAT1 represents a promising therapeutic target for osteosarcoma treatment.

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