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

癌症衍生的外泌体 lncRNA SNHG3 通过 hnRNPC 介导 β-catenin 的 RNA 稳定性促进结直肠癌的转移

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作者:Ling Huang, Guang Yang, Yanfei Shao, Jing Sun, Xiao Yang, Hiju Hong, Batuer Aikemu, Galiya Yesseyeva, Shuchun Li, Chengsheng Ding, Xiaodong Fan, Sen Zhang, Junjun Ma, Minhua Zheng

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.

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