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TSP-1 is downregulated and inversely correlates with miR-449c expression in Cushing's disease

Jie Ren1, Changwei Gu2, Yong Yang3

  • 1Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.

Journal of Cellular and Molecular Medicine
|April 25, 2019
PubMed

Insights

Thrombospondin-1 (TSP-1) is downregulated in Cushing's disease. Restoring TSP-1 suppresses pituitary tumor growth by inhibiting miR-449c, suggesting lncTHBS1 may protect against disease development.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Cushing's disease pathogenesis involves pituitary corticotroph adenomas.
  • Thrombospondin-1 (TSP-1), an angioinhibitory factor, regulates cell interactions and tumorigenesis.
  • Reduced TSP-1 expression is observed in human pituitary corticotroph tumors.

Purpose of the Study:

  • To investigate the role of TSP-1 in pituitary adenoma tumor function.
  • To elucidate the regulatory mechanisms involving TSP-1, miR-449c, and lncTHBS1 in Cushing's disease.

Main Methods:

  • Overexpression of TSP-1 in murine AtT20 pituitary corticotroph tumor cells.
  • Assessment of proopiomelanocortin (POMC) transcription and adrenocorticotropic hormone (ACTH) secretion.
  • Analysis of miR-449c targeting of TSP-1 and lncTHBS1 interactions using RNA-immunoprecipitation.

Main Results:

  • TSP-1 overexpression decreased POMC transcription and ACTH secretion.
  • TSP-1 suppressed pituitary adenoma cell proliferation, migration, and invasion.
  • miR-449c directly inhibited TSP-1 expression, enhancing tumorigenesis.
  • Low TSP-1 and lncTHBS1 expression correlated with high miR-449c in patients.
  • lncTHBS1 associates with miR-449c, suggesting it acts as a negative regulator.

Conclusions:

  • TSP-1 plays a crucial role in suppressing pituitary adenoma growth and function.
  • miR-449c promotes tumorigenesis by targeting TSP-1.
  • lncTHBS1 may act as a competing endogenous RNA (ceRNA) for miR-449c, potentially inhibiting Cushing's disease progression.
Keywords:
ACTH-secreting pituitary adenomasCushing's diseaselncTHBS1miR-449cthrombospondin-1

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