Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis.
Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis.
复制标题
作者：
近年来研究发现具核梭杆菌（Fusobacterium nucleatum，Fn）与胃癌（gastric cancer，GC）的发生有关。癌症来源的外泌体含有关键的调控非编码RNA，是细胞间通讯的重要介质。然而，从Fn感染的GC细胞分泌的外泌体（Fn‐GCEx）的功能和调节机制仍不清楚。在这项研究中，Fn-GCEx增强了体外GC细胞的增殖、迁移和侵袭能力，以及体内肿瘤的生长和转移。HOTTIP在用Fn-GCEx处理的GC细胞中也上调。此外，HOTTIP的敲低减弱了受体GC细胞中Fn‐GCEx的作用。HOTTIP通过海绵状microRNA（miR）-885 - 3 p促进EphB 2表达，从而激活Fn-GCEx处理的GC细胞中的PI 3 K/AKT通路。总体而言，Fn感染诱导来自GC细胞的外泌体HOTTIP上调，其随后通过miR-885 - 3 p/EphB 2/PI 3 K/AKT轴促进GC进展。在此，我们确定了一个潜在的分子途径和GC的治疗靶点。在这项研究中，我们首次证明了由具核梭杆菌（Fn）感染引起的胃癌（GC）细胞分泌的外泌体的增加可以促进GC的进展。从机制上讲，我们的结果表明Fn感染诱导外泌体HOTTIP升高，并通过microRNA-885 - 3 p/EphB 2/PI 3 K/AKT途径促进未感染的GC细胞的增殖、迁移和侵袭。
Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer‐derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn‐GCEx) secreted from Fn‐infected GC cells remains unclear. In this study, Fn‐GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn‐GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn‐GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)‐885‐3p, thus activating the PI3K/AKT pathway in Fn‐GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR‐885‐3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC. In this study, we showed for the first time that the increase of exosomes secreted by gastric cancer (GC) cells caused by Fusobacterium nucleatum (Fn) infection can promote the progression of GC. Mechanistically, our results suggested that Fn infection induced the elevation of exosomal HOTTIP and promoted the proliferation, migration, and invasion of uninfected GC cells through the microRNA‐885‐3p/EphB2/PI3K/AKT pathway.
登录
查看更多内容
影响因子：
3.3
作者：
Gao, Qing;Liu, Wei;Li, Zongfang
通讯作者：
Li, Zongfang
DOI：
10.1186/s13046-019-1394-6
发表时间：
2019-09-18
影响因子：
11.3
作者：
Shang, Anquan;Wang, Weiwei;Li, Dong
通讯作者：
Li, Dong
EphB2 的刺激通过 PI3K/Akt 介导的糖原合成酶激酶 3β 失活来减弱 tau 磷酸化
影响因子：
4.6
作者：
Jiang J;Wang ZH;Qu M;Gao D;Liu XP;Zhu LQ;Wang JZ
通讯作者：
Wang JZ
LncRNA MT1JP 在胃癌中作为 ceRNA 通过与 miR-92a-3p 竞争性结合来调节 FBXW7
影响因子：
37.3
作者：
Zhang G;Li S;Lu J;Ge Y;Wang Q;Ma G;Zhao Q;Wu D;Gong W;Du M;Chu H;Wang M;Zhang A;Zhang Z
通讯作者：
Zhang Z
影响因子：
4.6
作者：
Chow A;Zhou W;Liu L;Fong MY;Champer J;Van Haute D;Chin AR;Ren X;Gugiu BG;Meng Z;Huang W;Ngo V;Kortylewski M;Wang SE
通讯作者：
Wang SE