Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL.

Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL.
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外泌体lncRNA SCIRT/miR-665转移通过抑制HEYL促进肺癌细胞转移

DOI:
10.1155/2021/9813773
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发表时间:
2021
影响因子:
--
通讯作者:
Ying K
Ying K
中科院分区:
医学3区
文献类型:
--
作者:
Wang Z;Lin M;He L;Qi H;Shen J;Ying K

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肺癌仍然是全球癌症相关死亡的主要原因。最近,外泌体等细胞外囊泡作为治疗诊断生物标志物的来源和肺癌进展的重要参与者引起了人们的极大兴趣。然而,特定的外泌体货物(例如非编码RNA)如何选择性地包装到外泌体中并促进肺癌进展仍不清楚。在这项研究中,我们发现 miR-665 是非小细胞肺癌 (NSCLC) 和小细胞肺癌 (SCLC) 患者中升高最多的外泌体 miRNA。我们进一步证明,lncRNA SCIRT 在癌细胞外泌体中也有所增加,并且可能在 hnRNPA1 的帮助下促进 miR-665 的外泌体负载。因此,外泌体 miR-665 通过靶向 Notch 下游转录因子 HEYL 促进肺癌细胞侵袭和迁移。此外,我们发现miR-665和SCIRT在肺癌患者的肿瘤组织和血浆中显着上调,并且两者在转移性疾病样本中均表现出表达增加。我们的研究结果表明,miR-665 和 SCIRT 的外泌体转移是一种功能性和机制驱动的途径,有助于癌症进展,因此可能为肺癌提供新的诊断和治疗靶点。
Lung cancer remains the leading cause of cancer-related death worldwide. Recently, extracellular vesicles such as exosomes have attracted considerable interest both as a source for theranostic biomarkers and an essential participant in lung cancer progression. However, how specific exosomal cargos, such as noncoding RNAs, are selectively packaged into exosomes and promote lung cancer progression remains unclear. In this study, we identified miR-665 as the most elevated exosomal miRNA from both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. We further demonstrated that lncRNA SCIRT was also increased in cancer cell exosomes and may facilitate the exosomal loading of miR-665 with the help of hnRNPA1. As a consequence, exosomal miR-665 promoted lung cancer cell invasion and migration by targeting Notch downstream transcription factor HEYL. In addition, we found that miR-665 and SCIRT were significantly upregulated in tumor tissue and plasma of patients with lung cancer, and both of them showed increased expression in metastatic disease samples. Our findings suggest that the exosomal transferring of miR-665 and SCIRT is a functional and mechanism-driven pathway that contributes to cancer progression and, thus, may provide novel diagnostic and therapeutic targets for lung cancer.
miR-665 通过靶向 PTPRB 减少 Hippo 信号传导,从而促进肝细胞癌细胞迁移、侵袭和增殖。
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