Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis

Sihai Liu1, Jing Zhang2, Ting Zheng3

  • 1Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, 430060, China.

Open Life Sciences
|April 5, 2021
PubMed
Abstract

Insights

Circular RNA circ_WWC3 inhibits osteosarcoma (OS) progression by increasing PDE7B levels through sponging miR-421. This finding offers a potential therapeutic target for OS treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized as key regulators in osteosarcoma (OS) development.
  • The specific role of circ_WWC3 in OS progression remained largely unexplored prior to this study.

Purpose of the Study:

  • To investigate the functional role and underlying molecular mechanisms of circ_WWC3 in osteosarcoma.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and RNase R assay were used to quantify RNA levels.
  • Cellular assays including colony formation, MTT, Transwell, and flow cytometry assessed proliferation, migration, invasion, and apoptosis.
  • Western blot analyzed protein expression, while dual-luciferase reporter assays elucidated miRNA-target interactions.
  • A murine xenograft model was employed for in vivo validation.

Main Results:

  • circ_WWC3 and PDE7B were found to be downregulated in OS tissues and cells compared to normal controls.
  • Overexpression of circ_WWC3 or PDE7B inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis in vitro.
  • circ_WWC3 positively regulated PDE7B by sponging miR-421, and miR-421 overexpression reversed the effects of circ_WWC3.
  • Inhibition of miR-421 promoted malignant behaviors by targeting PDE7B, and circ_WWC3 suppressed tumor growth in vivo.

Conclusions:

  • circ_WWC3 acts as a tumor suppressor in osteosarcoma.
  • Overexpression of circ_WWC3 inhibits OS development by upregulating PDE7B through the sponging of miR-421.

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