Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway.
Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway.
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DOI：
10.1186/s13046-021-02018-1
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发表时间：
2021-06-26
期刊：
影响因子：
--
通讯作者：
Watari H
中科院分区：
文献类型：
--
作者：
Dong P;Xiong Y;Konno Y;Ihira K;Kobayashi N;Yue J;Watari H
上皮-间质转化（EMT）和有氧糖酵解是癌症转移的基本过程。虽然越来越多的证据表明，EMT诱导和增强有氧糖酵解在人类癌症之间的关联，这两个条件在子宫内膜癌（EC）细胞的机制仍然不清楚。我们表征了糖酵解酶己糖激酶2（HK 2）在介导EMT和糖酵解中的作用和分子机制，并研究了非编码RNA DLEU 2通过上调HK 2表达对EMT和糖酵解刺激的贡献。HK 2在EC组织中高度表达，其表达与总生存率低相关。HK 2的过表达通过激活FAK及其下游的ERK 1/2信号通路，有效地促进EC细胞的EMT表型和有氧糖酵解。此外，microRNA-455（miR-455）通过直接与HK 2 mRNA相互作用并抑制其表达而充当肿瘤抑制因子。此外，DLEU 2在EC组织中显示出显著更高的表达，并且DLEU 2表达增加与总生存率更差相关。DLEU 2通过两种不同的机制在EC细胞中作为HK 2诱导的EMT和糖酵解的上游激活剂：（i）DLEU 2通过与miR-455竞争性结合诱导HK 2表达，以及（ii）DLEU 2还与EZH 2相互作用以沉默HK 2的直接抑制剂miR-181 a。这项研究确定DLEU 2作为EC细胞中HK 2驱动的EMT和糖酵解的上游激活剂，并为EC的潜在治疗提供了重要的机制见解。在线版本包含补充材料，可在10.1186/s13046-021-02018-1获得。
Epithelial-to-mesenchymal transition (EMT) and aerobic glycolysis are fundamental processes implicated in cancer metastasis. Although increasing evidence demonstrates an association between EMT induction and enhanced aerobic glycolysis in human cancer, the mechanisms linking these two conditions in endometrial cancer (EC) cells remain poorly defined. We characterized the role and molecular mechanism of the glycolytic enzyme hexokinase 2 (HK2) in mediating EMT and glycolysis and investigated how long noncoding RNA DLEU2 contributes to the stimulation of EMT and glycolysis via upregulation of HK2 expression. HK2 was highly expressed in EC tissues, and its expression was associated with poor overall survival. Overexpression of HK2 effectively promoted EMT phenotypes and enhanced aerobic glycolysis in EC cells via activating FAK and its downstream ERK1/2 signaling. Moreover, microRNA-455 (miR-455) served as a tumor suppressor by directly interacting with HK2 mRNA and inhibiting its expression. Furthermore, DLEU2 displayed a significantly higher expression in EC tissues, and increased DLEU2 expression was correlated with worse overall survival. DLEU2 acted as an upstream activator for HK2-induced EMT and glycolysis in EC cells through two distinct mechanisms: (i) DLEU2 induced HK2 expression by competitively binding with miR-455, and (ii) DLEU2 also interacted with EZH2 to silence a direct inhibitor of HK2, miR-181a. This study identified DLEU2 as an upstream activator of HK2-driven EMT and glycolysis in EC cells and provided significant mechanistic insights for the potential treatment of EC. The online version contains supplementary material available at 10.1186/s13046-021-02018-1.
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影响因子：
12.8
作者：
Choe SR;Kim YN;Park CG;Cho KH;Cho DY;Lee HY
通讯作者：
Lee HY
影响因子：
--
作者：
Anderson M;Marayati R;Moffitt R;Yeh JJ
通讯作者：
Yeh JJ
影响因子：
--
作者：
Ihira K;Dong P;Xiong Y;Watari H;Konno Y;Hanley SJ;Noguchi M;Hirata N;Suizu F;Yamada T;Kudo M;Sakuragi N
通讯作者：
Sakuragi N
DOI：
10.1016/j.bbrc.2017.11.123
发表时间：
2018-01-01
影响因子：
3.1
作者：
Gao, Xianzheng;Zhao, Huaying;Zhang, Mingzhi
通讯作者：
Zhang, Mingzhi
DOI：
10.26355/eurrev_201902_17097
发表时间：
2019-02-01
影响因子：
3.3
作者：
Li, X-C;Hai, J-J;Liu, L-J
通讯作者：
Liu, L-J