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Updated: Feb 12, 2026

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
Published on: February 18, 2016
MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway
1Department of Neurosurgery, the Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China. liangtiji889@163.com.
Objective:
Extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signal pathway participates in cell proliferation, cycle, and apoptosis. MiR-16 is down-regulated in the pituitary tumor. This study investigated the role and related mechanism of miR-16 on pituitary tumor proliferation, cycle, and apoptosis.
Patients And Methods:
Dual-luciferase reporter assay was conducted to demonstrate the targeted regulation between miR-16 and MEK1. MiiR-16, MEK1, p-ERK1/2, Survivin and Cyclin D1 expression were compared between normal embryonic pituitary cells, HP75 tumor cells. Flow cytometry detection measured cell proliferation and cycle. Cultured HP75 cells were divided into four groups: miR-NC, miR-16 mimic, si-NC, and si-MEK1. Expressions of miR-16, MEK1, p-ERK1/2, Survivin, and Cyclin D1 were compared, and cell proliferation, cycle, and apoptosis were tested by flow cytometry.
Results:
Bioinformatics analysis showed complementary binding sites between miR-16 and MEK1. Dual luciferase reporter assay validated the direct regulation between miR-16 and MEK1. Compared to that of normal pituitary tissues, significantly lower miR-16 expression, but higher MEK1 level were found in adenoma tissues. Compared to normal embryonic pituitary cells, the level of miR-16 was decreased, while the expressions of p-ERK1/2, Survivin, and Cyclin D1, along with cell proliferation or S or G2/M phase ratio were up-regulated in the group of HP75 cells. Transfection of miR-16 mimic or si-MEK1 remarkably suppressed the expressions of MEK1, p-ERK1/2, Survivin or Cyclin D1 in HP75 cells, inhibited cell proliferation and induced apoptosis and cycle arrest.
Conclusions:
MiR-16 inhibited ERK/MAPK pathway activity via the suppression of MEK1 expression, and further suppressed proliferation of pituitary tumor cells.
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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