Chen Lei, Wang Yuhai, He Jianqing, Zhang Chunlei, Chen Junhui, Shi Dongliang
Department of Neurosurgery, 101st Hospital of PLA (Wuxi Taihu Hospital), Clinical Medical School of Anhui Medical University, Wuxi, P.R. China.
Oncol Res. 2018 Oct 17;26(9):1419-1428. doi: 10.3727/096504018X15178768577951. Epub 2018 Feb 8.
miR-152 and lncRNA H19 have been frequently implicated in various cellular processes including cell proliferation, invasion, angiogenesis, and apoptosis. However, the interaction between miR-152 and H19 in glioma has never been reported. RT-qPCR was used to examine the expression of miR-152 and H19 in human glioma cell lines and normal human astrocytes (NHAs). The interaction between miR-152 and lncRNA H19 was assessed by dual-luciferase reporter assay. MTT assay and Transwell invasion assay were used to determine the proliferation and invasion of U251 and U87 cells. A xenograft tumor experiment was performed to confirm the role of H19 in vivo. The results showed that H19 expression was upregulated and miR-152 expression was downregulated in human glioma cell lines. H19 downregulation or miR-152 upregulation suppressed glioma cell proliferation and invasion in vitro. Moreover, H19 and miR-152 directly regulated each other. Furthermore, decreased miR-152 expression alleviated si-H19-induced inhibitory effects on proliferation and invasion in glioma cells. As expected, H19 silencing hindered glioma growth in vivo. Taken together, H19 promoted glioma cell proliferation and invasion by negatively regulating miR-152 expression, providing evidence for the potential application of H19 as a biomarker and therapy target for glioma.
miR - 152和长链非编码RNA H19频繁参与包括细胞增殖、侵袭、血管生成和凋亡在内的各种细胞过程。然而,miR - 152与H19在胶质瘤中的相互作用尚未见报道。采用RT - qPCR检测miR - 152和H19在人胶质瘤细胞系和正常人星形胶质细胞(NHA)中的表达。通过双荧光素酶报告基因检测评估miR - 152与长链非编码RNA H19之间的相互作用。采用MTT法和Transwell侵袭实验检测U251和U87细胞的增殖和侵袭能力。进行异种移植瘤实验以证实H19在体内的作用。结果显示,人胶质瘤细胞系中H19表达上调,miR - 152表达下调。下调H19或上调miR - 152可抑制体外胶质瘤细胞的增殖和侵袭。此外,H19与miR - 152相互直接调控。而且,miR - 152表达降低可减轻si - H19对胶质瘤细胞增殖和侵袭的抑制作用。正如预期的那样,沉默H19可抑制体内胶质瘤的生长。综上所述,H19通过负向调控miR - 152表达促进胶质瘤细胞增殖和侵袭,为H19作为胶质瘤生物标志物和治疗靶点的潜在应用提供了证据。