miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene.
miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene.
复制标题
DOI：
10.1186/s13046-018-0824-1
复制
发表时间：
2018-07-09
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Li Y;Zhang H;Gong H;Yuan Y;Li Y;Wang C;Li W;Zhang Z;Liu M;Liu H;Chen J
转移是癌症死亡率的主要原因，是肺癌治疗的主要障碍。 Invadopodia是癌症特异性的突出结构，通过降解地下膜和周围的基质在转移性级联反应中起着至关重要的作用。 Cortactin是Invadopodia的关键成分，经常用作Invadopodia标记，这是Invadopodia功能中普遍重要的玩家，并且经常在癌症中过表达，但是确切的调节机制尚未完全理解。
通过QRT-PCR检测到人非小细胞肺癌（NSCLC）组织中CTTN的表达水平。分别通过伤口愈合，Transwell分析和免疫荧光在体外评估细胞迁移，侵袭和侵袭性形成。双脂肪酸酶报告基测定器用于识别miR-182的直接靶标。
肝细胞生长因子（HGF）和佛波尔12,13-二甲酸酯（PDBU）可以诱导CTTN表达，运动性和侵袭能力，以及在非小细胞肺癌（NSCLC）中的Invadopodia形成。此外，miR-182通过靶向NSCLC中的CTTN抑制了转移和侵袭性形成。我们的QRT-PCR结果表明，CTTN表达与miR-182表达成反比，该表达通过抑制CDC42/N-WASP途径抑制了侵袭性的形成。此外，miR-182通过抑制colortactin抑制肺癌细胞中抑制细胞外基质（ECM）降解的受负调控的功能。
总的来说，我们的结果表明，miR-182在NSCLC中靶向CTTN基因，并抑制了肺癌Invadopodia形成，因此抑制了肺癌转移。这表明miR-182在NSCLC中的治疗应用。
本文的在线版本（10.1186/S13046-018-0824-1）包含补充材料，可供授权用户使用。
Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood. The expression level of CTTN in human non-small cell lung cancer (NSCLC) tissues was detected by qRT-PCR. Cell migration, invasion and invadopodia formation were assessed in vitro by wound-healing, transwell assay and immunofluorescence, respectively. The dual-luciferase reporter assay was used to identify the direct target of miR-182. Hepatocyte growth factor (HGF) and phorbol 12,13-dibutyrate (PDBu) can induce CTTN expression, motility, and invasion ability, as well as invadopodia formation in non-small cell lung cancer (NSCLC). Moreover, miR-182 suppressed metastasis and invadopodia formation by targeting CTTN in NSCLC. Our qRT-PCR results showed that CTTN expression was inversely correlated with miR-182 expression that suppressed invadopodia formation via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulated invadopodia function, and suppressed extracellular matrix(ECM) degradation in lung cancer cells by inhibiting cortactin. Collectively, our results demonstrated that miR-182 targeted CTTN gene in NSCLC and suppressed lung cancer invadopodia formation, and thus suppressed lung cancer metastasis. This suggests a therapeutic application of miR-182 in NSCLC. The online version of this article (10.1186/s13046-018-0824-1) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
8
作者：
Goicoechea, S. M.;Bednarski, B.;Garcia-Mata, R.;Prentice-Dunn, H.;Kim, H. J.;Otey, C. A.
通讯作者：
Otey, C. A.
影响因子：
4
作者：
Goicoechea, Silvia M.;Zinn, Ashtyn;Garcia-Mata, Rafael
通讯作者：
Garcia-Mata, Rafael
影响因子：
56.9
作者：
Lim, LP;Glasner, ME;Bartel, DP
通讯作者：
Bartel, DP
影响因子：
8.8
作者：
通讯作者：
--
MiR-146b-5p 在非小细胞肺癌中充当抑制 miRNA 和预后预测因子
影响因子：
3.9
作者：
Li Y;Zhang H;Dong Y;Fan Y;Li Y;Zhao C;Wang C;Liu J;Li X;Dong M;Liu H;Chen J
通讯作者：
Chen J