MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway

D-W Wang1, Y-Q Wang, H-S Shu

  • 1Department of Neurosurgery, the Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China. liangtiji889@163.com.

Abstract

Insights

MicroRNA-16 (miR-16) suppresses pituitary tumor growth by inhibiting the MEK1-ERK/MAPK pathway. Restoring miR-16 levels reduces tumor cell proliferation and induces apoptosis, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway is crucial for cell proliferation, cell cycle regulation, and apoptosis.
  • MicroRNA-16 (miR-16) is frequently downregulated in pituitary tumors, suggesting a potential role in tumorigenesis.

Purpose of the Study:

  • To investigate the role of miR-16 in pituitary tumor progression.
  • To elucidate the underlying molecular mechanisms by which miR-16 affects pituitary tumor cell proliferation, cell cycle, and apoptosis.

Main Methods:

  • Bioinformatics analysis and dual-luciferase reporter assays were used to confirm the direct targeting of MEK1 by miR-16.
  • Expression levels of miR-16, MEK1, p-ERK1/2, Survivin, and Cyclin D1 were compared between normal pituitary cells and HP75 pituitary tumor cells.
  • Flow cytometry was employed to assess cell proliferation, cell cycle distribution, and apoptosis in cultured HP75 cells following transfection with miR-16 mimics or MEK1-specific small interfering RNA (si-MEK1).

Main Results:

  • Bioinformatics and luciferase assays confirmed that miR-16 directly targets MEK1.
  • Pituitary adenoma tissues and HP75 cells exhibited significantly lower miR-16 expression and higher MEK1 levels compared to normal tissues and cells.
  • Overexpression of miR-16 or inhibition of MEK1 in HP75 cells led to decreased MEK1, p-ERK1/2, Survivin, and Cyclin D1 expression, suppressed cell proliferation, induced apoptosis, and caused cell cycle arrest.

Conclusions:

  • MiR-16 acts as a tumor suppressor in pituitary tumors by inhibiting the MEK1-ERK/MAPK signaling pathway.
  • Targeting miR-16 or its downstream effectors presents a potential therapeutic strategy for pituitary tumors.

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