The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1.
The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1.
复制标题
IncRNA MACC1-AS1通过AMPK/Lin28介导的MACC1 mRNA稳定性促进胃癌细胞代谢可塑性
DOI：
10.1186/s12943-018-0820-2
复制
发表时间：
2018-03-06
期刊：
影响因子：
37.3
通讯作者：
Shi M
中科院分区：
文献类型：
--
作者：
Zhao Y;Liu Y;Lin L;Huang Q;He W;Zhang S;Dong S;Wen Z;Rao J;Liao W;Shi M
代谢可塑性越来越被认为是肿瘤生长和转移的决定因素。MACC 1是MET的转录调控因子，是胃癌中的一个癌基因，但其转录或翻译后调控机制尚不清楚。我们先前报道了MACC 1在糖酵解中促进GC进展的代谢作用。MACC 1-AS 1是MACC 1的反义lncRNA，但其功能以前未知。我们利用TCGA数据库以及原位杂交分析了123对GC组织和匹配的正常胃粘膜组织（ANT）中MACC 1-AS 1的表达。通过进行体外和体内功能实验来确定MACC 1-AS 1在细胞生长和转移中的生物学作用。通过糖酵解和抗氧化能力的测定来考察其代谢功能。此外，MACC 1-AS 1对MACC 1的特异性调节作用在转录和转录后进行了探索。MACC 1-AS 1在胃癌组织中的表达显著高于ANT，这预示着胃癌患者的预后不良。MACC 1-AS 1在代谢应激下促进胃癌细胞增殖，抑制胃癌细胞凋亡。从机制上讲，MACC 1-AS 1稳定了MACC 1 mRNA，并在转录后增强了MACC 1表达。此外，MACC 1-AS 1显示通过MACC 1上调和随后增强的糖酵解和抗氧化能力来介导代谢可塑性，并且这被认为是由AMPK/Lin 28途径协调的。MACC 1-AS 1在胃癌组织中的高表达与不良预后相关，并促进癌细胞的恶性表型。MACC 1-AS 1在代谢应激下升高，并通过mRNA稳定促进MACC 1表达来促进代谢可塑性。我们的研究暗示lncRNA MACC 1-AS 1作为GC诊断和预后的有价值的生物标志物。本文的在线版本（10.1186/s12943-018-0820-2）包含补充材料，可供授权用户使用。
Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis. The online version of this article (10.1186/s12943-018-0820-2) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
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
DOI：
10.1016/j.neo.2015.08.005
发表时间：
2015-08
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Simões RV;Serganova IS;Kruchevsky N;Leftin A;Shestov AA;Thaler HT;Sukenick G;Locasale JW;Blasberg RG;Koutcher JA;Ackerstaff E
通讯作者：
Ackerstaff E
影响因子：
4.3
作者：
Wu, Zhen-Zhen;Chen, Li-Shan;Liao, Wang-Jun
通讯作者：
Liao, Wang-Jun
影响因子：
23.9
作者：
Shyh-Chang, Ng;Daley, George Q.
通讯作者：
Daley, George Q.