HBx-upregulated MAFG-AS1 promotes cell proliferation and migration of hepatoma cells by enhancing MAFG expression and stabilizing nonmuscle myosin IIA
HBx-upregulated MAFG-AS1 promotes cell proliferation and migration of hepatoma cells by enhancing MAFG expression and stabilizing nonmuscle myosin IIA
复制标题
HBx 上调的 MAFG-AS1 通过增强 MAFG 表达和稳定非肌肉肌球蛋白 IIA 来促进肝癌细胞的细胞增殖和迁移。
DOI：
10.1096/fj.202002374r
复制
发表时间：
2021-05-01
期刊：
影响因子：
4.8
通讯作者：
Ye, Xin
中科院分区：
文献类型：
--
作者：
Zhang, Fang;Li, Yong;Ye, Xin
为了鉴定与B型肝炎病毒（HBV）相关的lncRNA，我们之前通过RNA深度测序检查了HBV转基因细胞系HepG 2 - 4D 14和亲本HepG 2细胞的转录谱，并鉴定了38个上调的长非编码RNA（lncRNA）。在本研究中，lncRNA MAFG-AS 1的详细研究，因为它的基因位于邻近的MAFG基因，这是一个重要的转录因子参与细胞增殖。MAFG-AS 1在HCC组织中的表达水平显著高于非肿瘤组织。TCGA数据显示MAFG-AS 1的表达水平与HCC患者的生存率呈负相关。GEO队列数据显示，与健康组织相比，MAFG-AS 1在HBV感染的肝组织中的表达水平显著升高。实时荧光定量PCR和荧光素酶报告基因检测结果表明，HBx能增强MAFG-AS 1的转录。功能获得和功能丧失实验表明MAFG-AS 1促进HCC细胞的增殖、迁移和侵袭。肿瘤形成测定结果表明MAFG-AS 1的敲低显著抑制裸鼠中的细胞增殖。此外，MAFG-AS 1通过E2 F1增强相邻MAFG的转录。此外，MAFG-AS 1与非肌肉肌球蛋白IIA（NM IIA）的三个亚基（MYH 9、MYL 12 B和MYL 6）相互作用。MAFG-AS 1的敲低抑制MYH 9的ATP酶活性、NM IIA亚基的相互作用和细胞周期进程。因此，lncRNA MAFG-AS 1被HBV上调并促进HCC细胞的增殖和迁移。我们的研究结果表明，MAFG-AS 1是一个潜在的癌基因，可能有助于HBV相关的肝癌的发展。
To identify hepatitis B virus (HBV)-related lncRNA(s), we previously examined the transcription profiles of the HBV-transgenic cell line HepG2-4D14 and parental HepG2 cells by RNA deep sequencing and identified 38 upregulated long noncoding RNAs (lncRNAs). In the present study, the lncRNA MAFG-AS1 is investigated in detail because its gene is located adjacent to the MAFG gene, which is an important transcription factor involved in cell proliferation. The level of MAFG-AS1 is significantly higher in HCC tissue than in nontumor tissues. TCGA data show that the expression level of MAFG-AS1 is negatively correlated with survival of HCC patients. GEO cohort data show that compared with healthy tissues, the expression level of MAFG-AS1 is significantly higher in HBV-infected liver tissues. Real-time PCR and luciferase reporter assay data show that HBx can enhance the transcription of MAFG-AS1. Gain-of-function and loss-of-function experiments indicate that MAFG-AS1 promotes proliferation, migration, and invasion of HCC cells. Tumor formation assay results demonstrate that knockdown of MAFG-AS1 significantly inhibits cell proliferation in nude mice. Furthermore, MAFG-AS1 enhances the transcription of adjacent MAFG via E2F1. Additionally, MAFG-AS1 interacts with three subunits (MYH9, MYL12B, and MYL6) of nonmuscle myosin IIA (NM IIA). Knockdown of MAFG-AS1 inhibits ATPase activity of MYH9, interaction of NM IIA subunits, and cell cycle progression. Thus, the lncRNA MAFG-AS1 is upregulated by HBV and promotes proliferation and migration of HCC cells. Our findings suggest that MAFG-AS1 is a potential oncogene that may contribute to HBV-related HCC development.