Li Hongxing, Li Bo, Zhu Dongmei, Xie Hua, Du Chunxia, Xia Yankai, Tang Weibing
Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Oncotarget. 2017 Jul 12;8(41):69722-69730. doi: 10.18632/oncotarget.19207. eCollection 2017 Sep 19.
The long noncoding RNA (lncRNA) MEG3 is involved in various biological processes including cell migration and cell proliferation. In present study, it was found that MEG3 and the intronic miR-770-5p were decreased in samples from HSCR patients. Besides, knockdown of MEG3 and miR-770-5p suppressed cell migration and proliferation, while cell cycle and apoptosis were not affected in human 293T and SH-SY5Y cells. SRGAP1 mRNA and protein upregulation was inversely correlated with miR-770-5p expression in tissue samples and cell lines, which was confirmed to be a target gene of miR-770-5p by dual-luciferase reporter assay. Moreover, silencing of SRGAP1 rescued the inhibition of cell migration and proliferation induced by MEG3 siRNA and miR-770-5p inhibition. The present study elucidates a novel mechanism of the development of HSCR and shows that the MEG3/miR-770-5p/SRGAP1 pathway plays a vital role in the pathogenesis of HSCR.
长链非编码RNA(lncRNA)MEG3参与包括细胞迁移和细胞增殖在内的多种生物学过程。在本研究中,发现HSCR患者样本中MEG3和内含子miR-770-5p水平降低。此外,在人293T和SH-SY5Y细胞中,敲低MEG3和miR-770-5p可抑制细胞迁移和增殖,但不影响细胞周期和凋亡。在组织样本和细胞系中,SRGAP1 mRNA和蛋白上调与miR-770-5p表达呈负相关,双荧光素酶报告基因检测证实SRGAP1是miR-770-5p的靶基因。此外,沉默SRGAP1可挽救由MEG3 siRNA和miR-770-5p抑制所诱导的细胞迁移和增殖抑制。本研究阐明了HSCR发生发展的一种新机制,并表明MEG3/miR-770-5p/SRGAP1通路在HSCR发病机制中起重要作用。