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Tanshinone I restrains osteosarcoma progression by regulating circ_0000376/miR-432-5p/BCL2 axis

Baoguo Ye1, Kong Qiao2, Qiheng Zhao3

  • 1Department of Anesthesiology, China-Japan Union Hospital Jilin University, No. 126 Xiantai Street, Changchun City, 234000, Jilin Province, China.

Molecular and Cellular Biochemistry
|September 17, 2021
PubMed

Insights

Tanshinone I inhibits osteosarcoma progression by downregulating circ_0000376. This circular RNA (circRNA) targets miR-432-5p, upregulating BCL2, promoting cancer growth. Silencing circ_0000376 enhances anti-tumor effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) are emerging regulators in cancer progression.
  • The specific role of circ_0000376 in osteosarcoma (OS) remains largely uncharacterized.

Purpose of the Study:

  • To investigate the biological function of circ_0000376 in osteosarcoma (OS) progression.
  • To elucidate the underlying molecular mechanisms, including its interaction with microRNAs and target genes.
  • To evaluate the therapeutic potential of targeting circ_0000376 in combination with Tanshinone I (Tan I).

Main Methods:

  • Cell viability, colony formation, apoptosis, and motility assays were performed.
  • Cellular glycolytic metabolism was assessed using commercial kits.
  • RNA and protein expression were analyzed by RT-qPCR and Western blot.
  • circRNA-miRNA-mRNA interactions were predicted using Starbase and validated by dual-luciferase reporter assays.
  • Xenograft tumor assays were conducted in vivo.

Main Results:

  • Tanshinone I (Tan I) suppressed OS cell viability, migration, invasion, glycolysis, and induced apoptosis, while downregulating circ_0000376 expression.
  • Overexpression of circ_0000376 rescued the malignant behaviors of OS cells affected by Tan I.
  • Circ_0000376 acted as a sponge for miR-432-5p, leading to the upregulation of B-cell leukemia/lymphoma 2 (BCL2) expression.
  • Silencing circ_0000376 enhanced the anti-tumor effect of Tan I in xenograft models.

Conclusions:

  • Circ_0000376 promotes osteosarcoma progression by sponging miR-432-5p and upregulating BCL2.
  • Tan I exerts anti-tumor effects in OS by targeting the circ_0000376/miR-432-5p/BCL2 axis.
  • Circ_0000376 is a potential therapeutic target for osteosarcoma treatment.
Keywords:
BCL2OsteosarcomaTanshinone Icirc_0000376miR-432-5p

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