Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer.
Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer.
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Lnc-GAN1 表达与非小细胞肺癌的良好生存相关，并通过海绵 mir-26a-5p 激活 PTEN 信号传导来抑制肿瘤进展
DOI：
10.1186/s13046-020-01819-0
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发表时间：
2021-01-06
期刊：
影响因子：
--
通讯作者：
Wang HY
中科院分区：
文献类型：
--
作者：
Wang RQ;Long XR;Zhou NN;Chen DN;Zhang MY;Wen ZS;Zhang LJ;He FZ;Zhou ZL;Mai SJ;Wang HY
背景长非编码RNA(Long Non-Coding RNAs，LncRNAs)在非小细胞肺癌(NSCLC)的发生发展中起重要作用，但大多数LncRNAs在NSCLC中的作用尚不清楚。本研究探讨了lnc-GAN1在非小细胞肺癌中的临床意义、生物学功能及其机制。方法采用定制的lncRNA芯片，发现lnc-GAN1在非小细胞肺癌组织中表达明显下调。采用定量逆转录聚合酶链式反应检测LNC-GAN1在NSCLC组织和细胞系中的表达水平。生存评估采用Kaplan-Meier方法。体外和体内评价lnc-GAN1对肺癌细胞的生物学功能。RNA荧光原位杂交和亚细胞定位分析表明，lnc-GAN1在细胞内呈亚细胞分布。采用生物信息学方法预测受lnc-GAN1调控的miRNAs和信号通路。结果LNC-GAN1在肝癌组织中表达下调，肿瘤体积较大，总生存期和无瘤生存期较差；其异位表达抑制NSCLC细胞的增殖、集落形成和细胞周期进展，并诱导细胞凋亡；在NSCLC异种移植模型中，LNC-GAN1也抑制肿瘤生长。我们进一步证明了lnc-GAN1定位于细胞质中，其转录独立于其亲本基因GAN。在机制上，lnc-GAN1通过两个种子序列作为miR-26a-5p的海绵，这两个非编码RNA在非小细胞肺癌组织中呈负相关；我们进一步证明PTEN是miR-26a-5p的直接靶点，并通过激活PTEN来抑制细胞周期信号通路，其表达水平与NSCLC中miR-26a-5p水平呈负相关，而与lnc-GAN1水平呈正相关。结论LNC-GAN1表达下调与NSCLC患者的生存不良有关，其机制是通过海绵和抑制miR-26a-5p上调PTEN而发挥肿瘤抑制作用。本研究为非小细胞肺癌提供了一个潜在的预后生物标志物和治疗靶点。
BackgroundLong non-coding RNAs (lncRNAs) play vital roles in the development and progression of non-small-cell lung cancer (NSCLC); however, the role of most lncRNAs in NSCLC remains unknown. This study explored the clinical significance, biological function and underlying mechanism of lnc-GAN1 in NSCLC.MethodsWith a custom lncRNA microarray we found that lnc-GAN1 is markedly downregulated in NSCLC tissues. Then lnc-GAN1 expression level was measured using qRT-PCR in NSCLC tissues and cell lines. Survival was assessed using the Kaplan-Meier method. The biological functions of lnc-GAN1 in lung cancer cells were evaluated in vitro and in vivo. RNA fluorescence in situ hybridization and subcellular localization assays revealed the subcellular distribution of lnc-GAN1 in cells. Bioinformatic analysis was adopted to predict miRNAs and signaling pathways regulated by lnc-GAN1. RNA immunoprecipitation and Dual-luciferase reporter assays were used to assess the interaction between lnc-GAN1 and miR-26a-5p in lung cancer cells.Resultslnc-GAN1 is downregulated in HCC tissues and associated with larger tumor size and poor overall survival and disease-free survival; its ectopic expression suppresses cell proliferation, colony formation, and cell cycle progression and induces apoptosis in NSCLC cells; it also inhibits tumor growth in the NSCLC xenograft model. We further proved that lnc-GAN1 is localized in cytoplasm and transcribed independently from its parental gene GAN. Mechanistically, lnc-GAN1 acts as a sponge for miR-26a-5p by two seed sequences, and the two non-coding RNAs have a negative relationship in NSCLC tissues; we further prove that PTEN is a direct target of miR-26a-5p and lnc-GAN1 inhibits cell cycle signaling pathway by activating PTEN, whose expression level correlated negatively with miR-26a-5p level but positively with lnc-GAN1 level in NSCLC samples.ConclusionsLnc-GAN1 is downregulated and associated with poor survival of NSCLC patients, and mechanistically acts as a tumor suppressor via sponging and inhibiting miR-26a-5p to upregulate PTEN. This study provides a potential prognostic biomarker and treatment target for NSCLC.
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影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
DOI：
10.1016/j.lungcan.2012.02.017
发表时间：
2012-07
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Rausch SM;Gonzalez BD;Clark MM;Patten C;Felten S;Liu H;Li Y;Sloan J;Yang P
通讯作者：
Yang P
影响因子：
20.4
作者：
Castellano, Joan J.;Navarro, Alfons;Monzo, Mariano
通讯作者：
Monzo, Mariano
影响因子：
4
作者：
Lu, Wei;Han, Lei;Miao, JunYing
通讯作者：
Miao, JunYing
影响因子：
39
作者：
Patz, Edward F., Jr.;Pinsky, Paul;Gatsonis, Constantine;Sicks, JoRean D.;Kramer, Barnett S.;Tammemaegi, Martin C.;Chiles, Caroline;Black, William C.;Aberle, Denise R.
通讯作者：
Aberle, Denise R.