Long Noncoding RNA HEIH Promotes Colorectal Cancer Tumorigenesis via Counteracting miR-939‒Mediated Transcriptional Repression of Bcl-xL.
Long Noncoding RNA HEIH Promotes Colorectal Cancer Tumorigenesis via Counteracting miR-939‒Mediated Transcriptional Repression of Bcl-xL.
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长非编码RNA HEIH通过协同miR-939介导的Bcl-XL转录抑制促进结直肠癌肿瘤发生
DOI：
10.4143/crt.2017.226
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发表时间：
2018-07
影响因子：
4.6
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Cui C;Zhai D;Cai L;Duan Q;Xie L;Yu J
研究发现长链非编码RNA HEIH（lncRNA-HEIH）被上调并促进肝细胞癌肿瘤生长。然而，其在结直肠癌（CRC）中的临床意义、作用和作用机制尚不清楚。通过定量实时聚合酶链反应测量CRC组织和细胞系中的lncRNA-HEIH表达。采用细胞计数试剂盒-8、乙炔基脱氧尿苷掺入法、末端脱氧核苷酸转移酶dUTP缺口末端标记法和裸鼠移植瘤实验研究lncRNA-HEIH的作用。通过RNA pull-down、RNA免疫沉淀、染色质免疫沉淀和荧光素酶报告基因分析研究lncRNA-HEIH的作用机制。在这项研究中，我们发现lncRNA-HEIH在CRC组织和细胞系中显著增加。lncRNA-HEIH的表达与肿瘤大小、浸润深度和CRC患者的不良预后呈正相关。lncRNA-HEIH的增强表达在体外促进CRC细胞增殖并减少凋亡，并且在体内促进CRC肿瘤生长。而敲低lncRNA-HEIH在体外抑制CRC细胞增殖并诱导凋亡，在体内抑制CRC肿瘤生长。从机制上讲，lncRNA-HEIH与miR-939物理结合。lncRNA-HEIH与miR-939的相互作用破坏了miR-939与核因子κB（NF-κB）的结合，增加了NF-κB与Bcl-xL启动子的结合，促进了Bcl-xL的转录和表达。此外，大肠癌组织中Bcl-xL的表达与lncRNA-HEIH呈正相关。阻断lncRNA-HEIH和miR-939之间的相互作用消除了lncRNA-HEIH对CRC肿瘤发生的影响。这项研究表明，lncRNA-HEIH通过抵消miR-939 miR-939介导的Bcl-xL转录抑制促进CRC肿瘤发生，并表明lncRNA-HEIH可作为CRC的预后生物标志物和治疗靶点。
Studies have found that long noncoding RNA HEIH (lncRNA-HEIH) is upregulated and facilitates hepatocellular carcinoma tumor growth. However, its clinical significances, roles, and action mechanism in colorectal cancer (CRC) remains unidentified. lncRNA-HEIH expression in CRC tissues and cell lines was measured by quantitative real-time polymerase chain reaction. Cell CountingKit-8, ethynyl deoxyuridine incorporation assay, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and nude mice xenografts assays were performed to investigate the roles of lncRNA-HEIH. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assays were performed to investigate the action mechanisms of lncRNA-HEIH. In this study, we found that lncRNA-HEIH is significantly increased in CRC tissues and cell lines. lncRNA-HEIH expression is positively associated with tumor size, invasion depth, and poor prognosis of CRC patients. Enhanced expression of lncRNA-HEIH promotes CRC cell proliferation and decreases apoptosis in vitro, and promotes CRC tumor growth in vivo. Whereas knockdown of lncRNA-HEIH inhibits CRC cell proliferation and induces apoptosis in vitro, and suppresses CRC tumor growth in vivo. Mechanistically, lncRNA-HEIH physically binds to miR-939. The interaction between lncRNA-HEIH and miR-939 damages the binding between miR-939 and nuclear factor κB (NF-κB), increases the binding of NF-κB to Bcl-xL promoter, and promotes the transcription and expression of Bcl-xL. Moreover, Bcl-xL expression is positively associatedwith lncRNA-HEIH in CRC tissues. Blocking the interaction between lncRNA-HEIH and miR-939 abolishes the effects of lncRNA-HEIH on CRC tumorigenesis. This study demonstrated that lncRNA-HEIH promotes CRC tumorigenesis through counteracting miR-939‒mediated transcriptional repression of Bcl-xL, and suggested that lncRNA-HEIH may serve as a prognostic biomarker and therapeutic target for CRC.
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影响因子：
21.3
作者：
Lin A;Li C;Xing Z;Hu Q;Liang K;Han L;Wang C;Hawke DH;Wang S;Zhang Y;Wei Y;Ma G;Park PK;Zhou J;Zhou Y;Hu Z;Zhou Y;Marks JR;Liang H;Hung MC;Lin C;Yang L
通讯作者：
Yang L
影响因子：
13.5
作者：
Yang, Fu;Zhang, Ling;Sun, Shu-han
通讯作者：
Sun, Shu-han
影响因子：
--
作者：
Cui, Chunhui;Yu, Jinlong;Huang, Zonghai
通讯作者：
Huang, Zonghai
DOI：
10.1073/pnas.0707594105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Place, Robert F.;Li, Long-Cheng;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
5.4
作者：
Zhu, Xiao-ting;Yuan, Ji-hang;Cheng, Xiao-yang
通讯作者：
Cheng, Xiao-yang