癌相关成纤维细胞衍生的细胞外囊泡将长链非编码RNA MAPKAPK5-AS1转运至肝癌细胞中并促进恶性细胞增殖。
CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation.
作者信息
Sheng Lin, Lin Junmei, Zhang Yili, Chen Yanping, Ye Xuxing, Wang Xiaobo
机构信息
The department of internal medicine, Jinhua Municipal Central Hospital, Jinhua, China.
Department of Traditional Chinese Medicine, Jinhua Municipal Central Hospital, Jinhua, China.
出版信息
Commun Biol. 2024 Dec 30;7(1):1711. doi: 10.1038/s42003-024-07428-3.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. LncRNA MAPKAPK5-AS1 is a potential oncogene and contributes to HCC cell malignant proliferation. This study explores the role of MAPKAPK5-AS1 carried by carcinoma-associated fibroblasts-derived extracellular vesicles (CAF-EVs) in HCC cell proliferation. Our findings reveal that CAF-EVs promotes HCC cell proliferation by delivering MAPKAPK5-AS1, which binds to and inhibits SMURF2 and stabilizes TCF12. SMURF2 leads to TCF12 ubiquitination and degradation. TCF12 upregulates FOXH1 expression. In animal model, CAF-EVs enhances tumor growth by stabilizing TCF12 via MAPKAPK5-AS1 and activating FOXH1 transcription. In conclusion, CAF-EVs carrying MAPKAPK5-AS1 stabilizes TCF12 expression by competitively inhibiting SMURF2, thus promoting TCF12-mediated FOXH1 transcription and driving HCC cell proliferation. Our findings may offer insights for HCC treatment and suggest potential targets for future treatments, opening avenues for HCC therapies.
肝细胞癌（HCC）是一种侵袭性恶性肿瘤，预后较差。长链非编码RNA MAPKAPK5-AS1是一种潜在的癌基因，促进肝癌细胞的恶性增殖。本研究探讨了癌相关成纤维细胞衍生的细胞外囊泡（CAF-EVs）携带的MAPKAPK5-AS1在肝癌细胞增殖中的作用。我们的研究结果表明，CAF-EVs通过传递MAPKAPK5-AS1促进肝癌细胞增殖，MAPKAPK5-AS1与SMURF2结合并抑制其活性，从而稳定TCF12。SMURF2导致TCF12泛素化和降解。TCF12上调FOXH1表达。在动物模型中，CAF-EVs通过MAPKAPK5-AS1稳定TCF12并激活FOXH1转录来促进肿瘤生长。总之，携带MAPKAPK5-AS1的CAF-EVs通过竞争性抑制SMURF2来稳定TCF12表达，从而促进TCF12介导的FOXH1转录并驱动肝癌细胞增殖。我们的研究结果可能为肝癌治疗提供见解，并为未来治疗提出潜在靶点，为肝癌治疗开辟新途径。
Zotero 插件