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Knockdown of long non-coding RNA TP73-AS1 inhibits osteosarcoma cell proliferation and invasion through sponging

Guangling Yang1, Ruipeng Song1, Limin Wang1

  • 1Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|June 6, 2018
PubMed

Insights

Long non-coding RNA TP73-AS1 is elevated in osteosarcoma (OS) and promotes tumor growth by sponging miR-142, leading to increased Rac1. Targeting TP73-AS1 may offer a new therapeutic strategy for OS.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) play critical roles in various cancers.
  • The role and mechanism of lncRNA TP73-AS1 in osteosarcoma (OS) remain largely uncharacterized.
  • Understanding lncRNA functions is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the expression and functional role of lncRNA TP73-AS1 in osteosarcoma.
  • To elucidate the underlying molecular mechanism of TP73-AS1 in OS progression.
  • To evaluate TP73-AS1 as a potential therapeutic target for osteosarcoma.

Main Methods:

  • Quantitative real-time PCR to assess TP73-AS1 expression in OS tissues and cell lines.
  • In vitro assays (proliferation, invasion) and in vivo tumor growth experiments following TP73-AS1 knockdown.
  • MiRNA target prediction and validation (e.g., luciferase reporter assay) to confirm miR-142 as a direct target.
  • Western blot analysis to assess the regulation of downstream targets like Rac1.

Main Results:

  • TP73-AS1 expression was significantly upregulated in OS tissues and cell lines compared to normal controls.
  • High TP73-AS1 expression correlated with poorer overall survival in OS patients.
  • Knockdown of TP73-AS1 inhibited OS cell proliferation and invasion in vitro and suppressed tumor growth in vivo.
  • TP73-AS1 directly targets and sponges miR-142, and inhibition of miR-142 reversed the effects of TP73-AS1 knockdown.
  • TP73-AS1 positively regulates Rac1 expression in OS cells via sponging miR-142.

Conclusions:

  • TP73-AS1 acts as an oncogenic lncRNA in osteosarcoma progression.
  • The TP73-AS1/miR-142/Rac1 axis is a key pathway in OS development.
  • TP73-AS1 represents a promising therapeutic target for osteosarcoma treatment.
Keywords:
OsteosarcomaRac1TP73-AS1miR-142

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