sh-lncRNA-SNHG4 Regulates Cell Proliferation, Apoptosis, and EMT in Osteosarcoma Cells via Regulating miR-204-5p to

Zhennan Tian1, Huilei Qiu1, Yaoguo Lang2

  • 1Pathology Department, Harbin Medical University Cancer Hospital, Harbin 150000, China.

Abstract

Insights

Long non-coding RNA SNHG4 promotes osteosarcoma (OS) progression by sponging miR-204-5p, leading to increased LRP8 expression and epithelial-mesenchymal transition (EMT). Inhibiting SNHG4 or restoring miR-204-5p suppresses OS growth and EMT.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma (OS) is a primary bone malignancy.
  • The epithelial-mesenchymal transition (EMT) is crucial for OS progression and metastasis.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.

Purpose of the Study:

  • To investigate the functional role of the lncRNA SNHG4/miR-204-5p/LRP8 axis in osteosarcoma.
  • To elucidate the involvement of this axis in the epithelial-mesenchymal transition (EMT) process in OS.

Main Methods:

  • Assessed SNHG4 expression in OS cell lines.
  • Utilized lentiviral vectors for gene expression manipulation (SNHG4, LRP8, miR-204-5p).
  • Evaluated cell proliferation, migration, invasion, and apoptosis using CCK-8, Transwell, and flow cytometry.
  • Confirmed targeting interactions using dual-luciferase reporter assays.
  • Validated findings in vivo using a xenograft tumor model in nude mice.

Main Results:

  • SNHG4 was highly expressed in OS cells, particularly in the 143B cell line.
  • Interference with SNHG4 or LRP8, or overexpression of miR-204-5p, inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
  • This axis was shown to promote EMT and activate the Wnt/β-catenin pathway.
  • In vivo studies confirmed that targeting this pathway significantly inhibited tumor growth and EMT.

Conclusions:

  • lncRNA SNHG4 acts as an oncogene in OS, promoting tumor progression and EMT.
  • miR-204-5p functions as a tumor suppressor within this axis.
  • The SNHG4/miR-204-5p/LRP8 axis is a critical regulator of OS development and EMT.
  • This axis represents a potential therapeutic target for osteosarcoma treatment.

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