LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation.
LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation.
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DOI：
10.1186/s13046-021-01990-y
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Peng X;Li X;Yang S;Huang M;Wei S;Ma Y;Li Y;Wu B;Jin H;Li B;Tang S;Fan Q;Liu J;Yang L;Li H
已知肿瘤细胞释放大量含有参与癌症进展的活性物质的外泌体。已证实异常表达的长链非编码RNA（lncRNA）调节与肿瘤进展相关的多个过程。然而，lncRNA影响外泌体分泌的机制仍不清楚。通过基因集富集分析（GSEA）、免疫印迹、纳米颗粒跟踪分析、共聚焦共定位分析、电子显微镜和侵袭实验确定了长非编码RNA LINC00511（LINC00511）调节多泡体（MVB）运输、外泌体分泌、侵袭伪足形成和肿瘤侵袭的潜在机制。我们发现，在肝细胞癌（HCC）中，肿瘤发生过程与囊泡分泌的显著增加有关。此外，LINC00511在HCC组织中显著更高表达，并且与囊泡运输和MVB分布相关。我们还发现，除了在HCC进展中形成侵袭伪足之外，异常LINC00511还通过调节囊泡相关膜蛋白7（VAMP 7）和突触体相关蛋白23（SNAP 23）的共定位来诱导HCC细胞中的侵袭伪足形成，从而诱导侵袭伪足形成，这是MVB的关键分泌位点并控制外泌体分泌。最后，我们揭示了LINC0051诱导的侵袭伪足和外泌体分泌参与肿瘤进展。我们的实验揭示了HCC中LINC00511失调与侵袭伪足产生和外泌体分泌之间关系的新发现。这是LINC00511调节侵袭伪足生物发生和外泌体分泌以进一步促进癌症进展的新机制。在线版本包含补充材料，可在10.1186/s13046 - 021 - 01990-y获得。
Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression. The online version contains supplementary material available at 10.1186/s13046-021-01990-y.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.8
作者：
Guo, Futao;Su, Zhangwen;Hu, Haiqing
通讯作者：
Hu, Haiqing
影响因子：
30.8
作者：
Gissen, P;Johnson, CA;Maher, ER
通讯作者：
Maher, ER
影响因子：
8.4
作者：
Manmi, Kawa;Wang, Qianxi
通讯作者：
Wang, Qianxi