METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner.
METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m(6)A-dependent manner.
复制标题
胃L16通过下调RAB 11 B-AS 1以m（6）A依赖的方式促进肝细胞癌进展。
DOI：
10.1186/s11658-022-00342-8
复制
发表时间：
2022-05-20
影响因子：
8.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肝细胞癌（HCC）的分子机制尚不清楚。N6-甲基腺苷（m6 A）作为一种主要的表位修饰，在肝癌的发生发展中起着重要的作用。本研究的目的是探讨RNA甲基转移酶甲基转移酶样蛋白16（RNA methyltransferase methyltransferase-like protein 16，缩写为L16）在肝细胞癌中的表达、作用和作用机制。RT-qPCR检测胃L16和RAB 11B-AS 1的表达。通过RNA免疫沉淀（RIP）、甲基化RIP（MeRIP）和RNA稳定性试验研究了胃L16对RAB 11B-AS 1的调节。进行了体外和体内功能获得和丧失试验，以研究胃L16和RAB 11 B-AS 1的作用。胃L16在肝癌组织中表达上调，其表达增加与肝癌患者的不良预后相关。在体内实验中，L16可促进肝癌细胞增殖、迁移和侵袭，抑制肝癌细胞凋亡，促进肝癌生长。胃L16可直接与长链非编码RNA（lncRNA）RAB 11B-AS 1结合，诱导RAB 11B-AS 1的m6 A修饰，降低RAB 11B-AS 1转录本的稳定性，导致RAB 11B-AS 1表达下调。与胃L16相反，RAB 11B-AS 1在HCC中表达下调，并且其表达降低与HCC患者的不良预后相关。肝癌组织中RAB 11B-AS 1与胃L16的表达呈负相关。RAB 11B-AS 1抑制肝癌细胞增殖、迁移和侵袭，促进肝癌细胞凋亡，抑制肝癌生长。功能性拯救试验显示，RAB 11 B-AS 1的过表达逆转了胃L16在HCC中的致癌作用。本研究确定了HCC中的胃L16/RAB 11 B-AS 1调节轴，这代表了HCC预后和治疗的新靶点。在线版本包含补充材料，可通过10.1186/s11658-022-00342-8获得。
The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m6A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment. The online version contains supplementary material available at 10.1186/s11658-022-00342-8.
登录
查看更多内容
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
50.3
作者：
Dong, Lihui;Chen, Chuanyuan;Han, Dali
通讯作者：
Han, Dali
RNA甲基化N6-甲基腺苷调节剂对黑色素瘤恶性进展和预后的影响。
影响因子：
5.8
作者：
Liu J;Zhou Z;Ma L;Li C;Lin Y;Yu T;Wei JF;Zhu L;Yao G
通讯作者：
Yao G
影响因子：
14.8
作者：
Jia, Guifang;Fu, Ye;Zhao, Xu;Dai, Qing;Zheng, Guanqun;Yang, Ying;Yi, Chengqi;Lindahl, Tomas;Pan, Tao;Yang, Yun-Gui;He, Chuan
通讯作者：
He, Chuan
影响因子：
--
作者：
Li, Tiegang;Wu, Di;Lu, Jiachun
通讯作者：
Lu, Jiachun