FEZF1-AS1/miR-107/ZNF312B axis facilitates progression and Warburg effect in pancreatic ductal adenocarcinoma.
FEZF1-AS1/miR-107/ZNF312B axis facilitates progression and Warburg effect in pancreatic ductal adenocarcinoma.
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FEZF1-AS1/miR-107/ZNF312B轴促进胰腺导管腺癌的进展和Warburg效应
DOI：
10.1038/s41419-017-0052-1
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发表时间：
2018-01-18
影响因子：
9
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Ye H;Zhou Q;Zheng S;Li G;Lin Q;Ye L;Wang Y;Wei L;Zhao X;Li W;Fu Z;Liu Y;Li Z;Chen R
长链非编码RNA（lncRNA）在病理过程中起着关键作用。然而，关于lncRNA在胰腺导管腺癌（PDAC）中的潜在功能和机制的信息很少。新的lncRNA FEZF 1-AS 1及其有义同源基因ZNF 312 B在人PDAC组织和细胞系中高表达，其与疾病进展相关并预测PDAC患者的临床结果。值得注意的是，生物信息学分析、荧光素酶测定和RNA免疫沉淀测定表明，FEZF 1-AS 1可能通过竞争miR-107而充当内源性海绵，从而调节ZNF 312 B的去阻遏。下调FEZF 1-AS 1或ZNF 312 B可显著抑制PDAC细胞的体外增殖、集落形成、迁移和侵袭，而miR-107抑制剂可消除下调FEZF 1-AS 1或ZNF 312 B降低PDAC细胞致癌能力的作用。此外，FEZF 1-AS 1/miR-107/ZNF 312 B轴诱导PDAC细胞增殖可能是通过调节细胞凋亡和G1-S检查点来介导的。此外，FEZF 1-AS 1的下调抑制了小鼠异种移植模型中的肿瘤生长。特别地，我们的结果突出了FEZF 1-AS 1/miR-107/ZNF 312 B轴对PDAC细胞的瓦尔堡效应维持的贡献。总的来说，我们的研究结果表明，FEZF 1-AS 1/miR-107/ZNF 312 B轴调控网络可能为PDAC提供潜在的新治疗策略。
Long non-coding RNAs (lncRNAs) play a pivotal role in pathological processes. However, little information has been published regarding the underlying functions and mechanisms of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). A novel lncRNA FEZF1-AS1 and its sense-cognate gene ZNF312B were found to be highly expressed in human PDAC tissues and cell lines, which is associated with disease progression and predicts clinical outcome in PDAC patients. Of note, bioinformatics analysis, luciferase assays and RNA immunoprecipitation assays indicated that FEZF1-AS1 may act as an endogenous sponge by competing for miR-107, thereby modulating the derepression of ZNF312B. Downregulation of FEZF1-AS1 or ZNF312B significantly inhibited proliferation, colony formation, migration, and invasion of PDAC cells in vitro, whereas the miR-107 inhibitor abrogated the effect of dow-regulation of FEZF1-AS1 or ZNF312B in reducing oncogenic capacities of PDAC cells. In addition, FEZF1-AS1/miR-107/ZNF312B axis-induced promotion of PDAC cells proliferation appeared to be mediated by modulation of the apoptosis and the G1-S checkpoint. Furthermore, downregulation of FEZF1-AS1 repressed tumor growth in mouse xenograft models. In particular, our results highlight the contribution of FEZF1-AS1/miR-107/ZNF312B axis to Warburg effect maintenance of PDAC cells. Collectively, our findings demonstrate that the FEZF1-AS1/miR-107/ZNF312B axis regulatory network might provide a potential new therapeutic strategy for PDAC.
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影响因子：
37.3
作者：
Gibb EA;Brown CJ;Lam WL
通讯作者：
Lam WL
长非编码 RNA HOTTIP 通过调节 HOXA13 促进胰腺癌进展和吉西他滨耐药
影响因子：
7.4
作者：
Li Z;Zhao X;Zhou Y;Liu Y;Zhou Q;Ye H;Wang Y;Zeng J;Song Y;Gao W;Zheng S;Zhuang B;Chen H;Li W;Li H;Li H;Fu Z;Chen R
通讯作者：
Chen R
影响因子：
254.7
作者：
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通讯作者：
Jemal, Ahmedin
影响因子：
11.2
作者：
Tsai MC;Spitale RC;Chang HY
通讯作者：
Chang HY
影响因子：
2.6
作者：
Hashimoto, H;Yabe, T;Hibi, M
通讯作者：
Hibi, M