THBS2, a microRNA‑744‑5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors

Jiao,Heng; Zeng,Lingxiao; Zhang,Jianpeng; Yang,Shengsheng; Lou,Wenhui

doi:10.3892/ol.2020.11273

THBS2, a microRNA‑744‑5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors

Authors:
- Heng Jiao
- Lingxiao Zeng
- Jianpeng Zhang
- Shengsheng Yang
- Wenhui Lou
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Affiliations: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, P.R. China
Published online on: January 9, 2020 https://doi.org/10.3892/ol.2020.11273
Pages: 1683-1692
Copyright: © Jiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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