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肿瘤来源的外泌体 lncRNA SNHG3 通过 hnRNPC 介导β-catenin 的 RNA 稳定性促进结直肠癌的转移。

Cancer-derived exosomal lncRNA SNHG3 promotes the metastasis of colorectal cancer through hnRNPC-mediating RNA stability of β-catenin.

机构信息

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Int J Biol Sci. 2024 Apr 8;20(7):2388-2402. doi: 10.7150/ijbs.88313. eCollection 2024.

Abstract

Metastasis is the leading cause of death in colorectal cancer (CRC) patients. By mediating intercellular communication, exosomes exhibit considerable value in regulating tumor metastasis. Long non-coding RNAs (lncRNAs) are abundant in exosomes and participate in regulating tumor progression. However, it is poorly understood how the cancer-secreted exosomal lncRNAs affect CRC proliferation and metastasis. Here, by analyzing the public databases we identified a lncRNA SNHG3 and demonstrated that SNHG3 was delivered through CRC cells-derived exosomes to promote metastasis in CRC. Mechanistically, exosomal SNHG3 was internalized by CRC cells and afterward upregulated the expression of β-catenin by facilitating the intranuclear transport of hnRNPC. Consequently, the RNA stability of β-catenin was enhanced which led to the activation of EMT and metastasis of CRC cells. Our findings expand the oncogenic mechanisms of exosomal SNHG3 and identify it as a diagnostic marker for CRC.

摘要

转移是结直肠癌 (CRC) 患者死亡的主要原因。外泌体通过介导细胞间通讯,在调节肿瘤转移方面具有重要价值。长链非编码 RNA (lncRNA) 在 exosomes 中丰富,并参与调节肿瘤进展。然而,目前尚不清楚癌细胞分泌的 exosomal lncRNA 如何影响 CRC 的增殖和转移。在这里,通过分析公共数据库,我们鉴定了一个 lncRNA SNHG3,并证实 SNHG3 通过 CRC 细胞衍生的外泌体传递,以促进 CRC 的转移。从机制上讲,外泌体 SNHG3 被 CRC 细胞内化,并通过促进 hnRNPC 的核内转运来上调β-catenin 的表达。因此,β-catenin 的 RNA 稳定性增强,导致 EMT 的激活和 CRC 细胞的转移。我们的研究结果扩展了外泌体 SNHG3 的致癌机制,并将其鉴定为 CRC 的诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c353/11077369/3a607ef0980a/ijbsv20p2388g001.jpg

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