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T3 Promotes Glioma Cell Senescence and Apoptosis via THRA and THRB.

Abstract
Glioma is one of the most common types of primary intracranial tumors. The relationship between triiodothyronine (T3) and glioma is not clear. This study aimed to investigate the effect of T3 on the proliferation of glioma cells and its mechanism. Cell viability was analyzed by cell counting kit 8 assay. Flow cytometry analysis was used to detect cell apoptosis and cell cycle. Thyroid hormone receptor α (THRA) and thyroid hormone receptor β (THRB) were silenced by transfecting si-THRA and si-THRB plasmids into HS683 and A172 glioma cells. Western blot was performed to assess the protein expressions. The results indicated that triiodothyronine (T3) affected the viability, apoptosis and cell cycle of HS683 and A172 glioma cells. Cell apoptosis was significantly inhibited in si-THRA and si-THRB experimental groups. Moreover, knockdown of THRA and THRB reversed the G1 and G2 phase arrest led by T3 and induced an up-regulation of cyclin D1 expression. The phosphorylated extracellular signal-regulated kinase (p-ERK), p-AKT, and phosphorylated signal transducer and activator of transcription (p-STAT3) proteins were markedly increased by inhibiting THRA and THRB in HS683 and A172 glioma cells. T3 affected apoptosis and cell cycle of glioma cells through regulating THRA and THRB expressions. THRA and THRB may affect glioma development through regulating, at least partially, the mitogen-activated protein kinase (MAPK)/ERK and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways.
AuthorsXingkui Zhang, Wei Ma, Junjun Li, Chunyan Li, Wei Liu, Zhiwei Tang, Liyan Li
JournalJournal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer (J Environ Pathol Toxicol Oncol) Vol. 40 Issue 4 Pg. 1-9 ( 2021) ISSN: 2162-6537 [Electronic] United States
PMID34936295 (Publication Type: Journal Article)
Chemical References
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • thyroid hormone receptor alpha, human
  • Triiodothyronine
Topics
  • Apoptosis (genetics)
  • Cell Line, Tumor
  • Cellular Senescence (genetics)
  • Gene Silencing
  • Glioma (physiopathology)
  • Humans
  • Thyroid Hormone Receptors alpha (genetics, metabolism)
  • Thyroid Hormone Receptors beta (genetics, metabolism)
  • Triiodothyronine (metabolism)

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