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.

Oncology Letters
|March 21, 2020
PubMed

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.