Zhang Yuan-Yuan, Feng Hao-Miao
Department of Endocrinology, Eastern Medical District of Linyi People's Hospital, Linyi, China.
Department of General Surgery, Linyi People's Hospital, Linyi, China.
Cell Physiol Biochem. 2017;44(1):345-356. doi: 10.1159/000484906. Epub 2017 Nov 13.
BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously.
The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay.
MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells.
This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.
背景/目的：胰腺神经内分泌肿瘤（pNETs）是起源于胰岛细胞的罕见肿瘤。最近，lncRNA MEG3被报道为多种癌症中的肿瘤抑制因子。本研究旨在揭示MEG3对pNETs的功能影响，这在之前尚未被发现。
通过转染其特异性载体/shRNA或模拟物/抑制剂来改变BON1细胞中MEG3、miR-183和BRI3的表达。此后，分别通过台盼蓝染色、流式细胞术、蛋白质免疫印迹和Transwell实验评估细胞活力、凋亡、细胞周期相关因子和凋亡相关因子的蛋白质表达，以及细胞迁移和侵袭。
与三种正常细胞系（HEK293、CCL-153和EC-304）相比，MEG3在BON1和QGP-1细胞中低表达。MEG3过表达降低了BON1细胞的活力、侵袭和迁移能力，但显著诱导了凋亡。miR-183是MEG3的直接靶点，miR-183上调消除了MEG3过表达对BON1细胞的抗生长和抗转移作用。此外BRI3是miR-183的靶点，BRI3可能通过激活BON1细胞中的p38/ERK/AKT和Wnt/β-连环蛋白信号发挥促肿瘤作用。
本研究证明了MEG3在BON1细胞中的肿瘤抑制作用，可抑制肿瘤细胞的生长和转移。揭示了一种新的调控机制，即MEG3/miR-183/BRI3轴的调节可能在pNET中起关键作用。
