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Updated: Dec 25, 2025

An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
THBS2, a microRNA-744-5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors
Heng Jiao1, Lingxiao Zeng1, Jianpeng Zhang2
1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Abstract:
The underlying molecular mechanisms of pancreatic neuroendocrine tumor (pNET) development have not yet been clearly identified. The present study revealed that thrombospondin 2 (THBS2) was downregulated in pNET tissues and cells. Forced expression of THBS2 inhibited the proliferation and migration of pNET cells in vitro. MicroRNA(miR)-744-5p was indicated to be a direct regulator of THBS2. Upregulation of miR-744-5p potentially caused THBS2 repression. Furthermore, THBS2 inhibited the production of matrix metalloproteinase (MMP) MMP9 through suppressing the transcriptional activity of CUT-like homeobox 1 (CUX1). CUX1 and MMP9 mediated the effect of THBS2 on pNET proliferation and migration, respectively. The results of the present study revealed a mechanistic role for THBS2 in pNET proliferation and migration, indicating that THBS2 was downregulated by miR-744-5p and further affected the CUX1/MMP9 cascade, which promoted the development of pNET.
Insights
Thrombospondin 2 (THBS2) is downregulated in pancreatic neuroendocrine tumors (pNETs). Restoring THBS2 inhibits pNET cell growth and migration by regulating the CUX1/MMP9 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The molecular drivers of pancreatic neuroendocrine tumor (pNET) development remain incompletely understood.
- Identifying key regulatory pathways is crucial for therapeutic strategies.
Purpose of the Study:
- To elucidate the role of thrombospondin 2 (THBS2) in pancreatic neuroendocrine tumor (pNET) pathogenesis.
- To investigate the regulatory mechanisms involving microRNA-744-5p (miR-744-5p), THBS2, CUT-like homeobox 1 (CUX1), and matrix metalloproteinase 9 (MMP9) in pNETs.
Main Methods:
- Analysis of THBS2 expression in pNET tissues and cells.
- In vitro experiments assessing the impact of THBS2 overexpression on pNET cell proliferation and migration.
- Investigation of the regulatory relationship between miR-744-5p and THBS2.
- Assessment of the downstream effects of THBS2 on CUX1 transcriptional activity and MMP9 production.
Main Results:
- THBS2 was found to be downregulated in pNET tissues and cells.
- Forced expression of THBS2 significantly inhibited pNET cell proliferation and migration in vitro.
- miR-744-5p was identified as a direct repressor of THBS2.
- THBS2 suppressed MMP9 production by inhibiting CUX1 transcriptional activity.
- CUX1 and MMP9 were shown to mediate the effects of THBS2 on pNET proliferation and migration.
Conclusions:
- THBS2 plays a significant mechanistic role in regulating pancreatic neuroendocrine tumor (pNET) cell proliferation and migration.
- The miR-744-5p/THBS2/CUX1/MMP9 signaling cascade is implicated in pNET development, with THBS2 acting as a tumor suppressor.
- These findings highlight potential therapeutic targets for pNETs.
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