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Updated: Aug 9, 2025

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
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The malignancy of chordomas is enhanced via a circTLK1/miR-16-5p/Smad3 positive feedback axis

Jingbing Lou1,2, Hongliang Zhang1,2, Qingshan Huang1,2

  • 1Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People's Republic of China.

Cell Death Discovery
|February 15, 2023
PubMed

Insights

Circular RNAs (circRNAs) like circTLK1 regulate cancer. This study found circTLK1 promotes chordoma progression by forming a feedback loop with miR-16-5p and Smad3, suggesting therapeutic targeting.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) are key regulators in various cancers.
  • The specific roles of circRNAs in chordoma progression are not fully understood.
  • MicroRNAs (miRNAs) are known to regulate tumor suppressor pathways.

Purpose of the Study:

  • To investigate the role of circTLK1 in chordoma.
  • To elucidate the regulatory mechanism of circTLK1 in chordoma progression.
  • To identify potential therapeutic targets for chordoma.

Main Methods:

  • Bioinformatic analyses to identify circTLK1.
  • Cell culture and tissue analysis to assess circTLK1 expression and function.
  • RNA immunoprecipitation and chromatin immunoprecipitation sequencing to determine molecular interactions.
  • In vitro assays to evaluate cell proliferation and invasion.
  • Pharmacological inhibition using SIS3.

Main Results:

  • CircTLK1 expression is significantly upregulated in chordoma tissues and cells.
  • CircTLK1 knockdown inhibits chordoma cell proliferation and invasion.
  • CircTLK1 directly binds to miR-16-5p, sequestering its tumor-suppressive activity.
  • CircTLK1 knockdown leads to decreased Smad3 expression.
  • Smad3 positively regulates TLK1 expression, establishing a circTLK1/miR-16-5p/Smad3 positive feedback loop.
  • The Smad3 inhibitor SIS3 disrupts this feedback loop.

Conclusions:

  • CircTLK1 acts as an oncogene in chordoma by regulating the circTLK1/miR-16-5p/Smad3 feedback axis.
  • Targeting this feedback loop, potentially with Smad3 inhibitors like SIS3, represents a promising therapeutic strategy for chordoma.

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