THBS2是一种微小RNA - 744 - 5p的靶标，它在胰腺神经内分泌肿瘤中通过CUX1调节MMP9的表达。
THBS2, a microRNA-744-5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors.
作者信息
Jiao Heng, Zeng Lingxiao, Zhang Jianpeng, Yang Shengsheng, Lou Wenhui
机构信息
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.
出版信息
Oncol Lett. 2020 Mar;19(3):1683-1692. doi: 10.3892/ol.2020.11273. Epub 2020 Jan 9.
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 . 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.
胰腺神经内分泌肿瘤（pNET）发生发展的潜在分子机制尚未明确。本研究发现血小板反应蛋白2（THBS2）在pNET组织和细胞中表达下调。THBS2的过表达抑制了pNET细胞的增殖和迁移。微小RNA（miR）-744-5p被证实是THBS2的直接调节因子。miR-744-5p的上调可能导致THBS2表达受抑。此外，THBS2通过抑制类CUT同源框1（CUX1）的转录活性来抑制基质金属蛋白酶（MMP）-9的产生。CUX1和MMP9分别介导了THBS2对pNET增殖和迁移的影响。本研究结果揭示了THBS2在pNET增殖和迁移中的作用机制，表明THBS2被miR-744-5p下调，并进一步影响CUX1/MMP9信号级联反应，从而促进了pNET的发展。
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