Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission.
Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission.
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长非编码RNA RACGAP1P通过miR-345-5p/RACGAP1介导的线粒体裂变促进乳腺癌侵袭和转移
DOI：
10.1002/1878-0261.12866
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发表时间：
2021-03
影响因子：
6.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Zhou D;Ren K;Wang M;Wang J;Li E;Hou C;Su Y;Jin Y;Zou Q;Zhou P;Liu X
在这项研究中，我们阐明了RACGAP1P参与乳腺癌侵袭和转移的潜在机制。在乳腺癌细胞中，RACGAP1P可以竞争性地与靶向RACGAP1的miR-345-5P结合，从而上调RACGAP1。RACGAP1P过表达通过RACGAP1P/miR-345-5P/RACGAP1/Drp1网络促进线粒体分裂介导的细胞侵袭。长非编码RNA(LncRNAs)是多种癌症的关键分子，但其在乳腺癌发病机制中的作用尚不完全清楚。在此，我们通过基因芯片分析发现，RAC GTP酶激活蛋白1(RACGAP1)的假基因lncRNA RACGAP1P在乳腺癌组织中表达上调。定量逆转录聚合酶链式反应证实其在25对乳腺癌组织和8株乳腺细胞系中高表达。随后，我们发现RACGAP1P的表达与102例乳腺癌患者的淋巴结转移、远处转移、TNM分期和较短的生存期呈正相关。然后，设计了体外和体内实验，研究RACGAP1P在乳腺癌细胞系中的生物学功能和调控机制。RACGAP1P在MDA-MB-231和MCF7乳腺癌细胞中的过表达增强了它们的侵袭能力，并增强了它们的线粒体分裂。相反，Mdivi-1抑制线粒体分裂可以降低RACGAP1P过表达细胞系的侵袭能力。此外，RACGAP1P对线粒体分裂的促进作用依赖于其与其亲本基因RACGAP1的miR-345-5P的竞争结合，从而导致动力蛋白相关蛋白1(Drp1)的激活。总之，LncRNA RACGAP1P通过miR-345-5P/RACGAP1途径介导的线粒体分裂促进乳腺癌的侵袭和转移。
In this study, we illustrate the potential mechanism of RACGAP1P implicated in breast cancer invasion and metastasis. In breast cancer cells, RACGAP1P could competitively bind to miR‐345‐5p, which targets RACGAP1, and therefore up‐regulate RACGAP1. RACGAP1P overexpression promoted mitochondrial fission‐mediated cell invasion via the RACGAP1P/miR‐345‐5p/RACGAP1/Drp1 network. Long non‐coding RNAs (lncRNAs) are emerging as key molecules in various cancers, yet their potential roles in the pathogenesis of breast cancer are not fully understood. Herein, using microarray analysis, we revealed that the lncRNA RACGAP1P, the pseudogene of Rac GTPase activating protein 1 (RACGAP1), was up‐regulated in breast cancer tissues. Its high expression was confirmed in 25 pairs of breast cancer tissues and 8 breast cell lines by qRT‐PCR. Subsequently, we found that RACGAP1P expression was positively correlated with lymph node metastasis, distant metastasis, TNM stage, and shorter survival time in 102 breast cancer patients. Then, in vitro and in vivo experiments were designed to investigate the biological function and regulatory mechanism of RACGAP1P in breast cancer cell lines. Overexpression of RACGAP1P in MDA‐MB‐231 and MCF7 breast cell lines increased their invasive ability and enhanced their mitochondrial fission. Conversely, inhibition of mitochondrial fission by Mdivi‐1 could reduce the invasive ability of RACGAP1P‐overexpressing cell lines. Furthermore, the promotion of mitochondrial fission by RACGAP1P depended on its competitive binding with miR‐345‐5p against its parental gene RACGAP1, leading to the activation of dynamin‐related protein 1 (Drp1). In conclusion, lncRNA RACGAP1P promotes breast cancer invasion and metastasis via miR‐345‐5p/RACGAP1 pathway‐mediated mitochondrial fission.
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影响因子：
10.5
作者：
Noh JH;Kim KM;Abdelmohsen K;Yoon JH;Panda AC;Munk R;Kim J;Curtis J;Moad CA;Wohler CM;Indig FE;de Paula W;Dudekula DB;De S;Piao Y;Yang X;Martindale JL;de Cabo R;Gorospe M
通讯作者：
Gorospe M
DOI：
10.1093/bioinformatics/btr209
发表时间：
2011-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lin MF;Jungreis I;Kellis M
通讯作者：
Kellis M
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
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影响因子：
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作者：
Fu, L.;Dong, Q.;Li, Q.
通讯作者：
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影响因子：
8
作者：
Chattaragada MS;Riganti C;Sassoe M;Principe M;Santamorena MM;Roux C;Curcio C;Evangelista A;Allavena P;Salvia R;Rusev B;Scarpa A;Cappello P;Novelli F
通讯作者：
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