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外泌体SOX21-AS1通过吸附miR-451a调控EREG并促进胰腺导管腺癌的恶性进展。

Exosomal SOX21-AS1 Regulates EREG by Sponging miR-451a and Promotes the Malignancy of Pancreatic Ductal Adenocarcinoma.

作者信息

Yan Yong, Wang Jinyi, Xu Bin, Ni Jianming, Dai Tu, Wang Liying, Wang Hao, Hua Zhiyuan, Li Kuan, Zhou Yongping

机构信息

Department of Hepatobiliary Surgery, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

J Cancer. 2024 Apr 23;15(11):3321-3337. doi: 10.7150/jca.95014. eCollection 2024.

DOI:10.7150/jca.95014
PMID:38817864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11134441/
Abstract

The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have increased. Exosomes, as a regulatory mode of intercellular communication, contain lncRNAs. SOX21-AS1 has been studied in other cancers, and its expression is elevated in PDAC, but its role in PDAC remains unclear. First, we analyzed the expression of lncRNAs in PDAC tissues and nontumor tissues through the TCGA database. Next, the results of the RT-qPCR experiment confirmed the prediction that the expression of SOX21-AS1 was elevated in PDAC tissues. and cell function assays confirmed that the degree of malignancy of PDAC was proportional to the expression of SOX21-AS1. In addition, through exosome isolation and uptake experiments, we first found that PDAC could secrete exosomal SOX21-AS1 and play an angiogenic role in HUVECs. Subsequently, the relationship between SOX21-AS1, miR-451a and epiregulin (EREG) was verified through database prediction and analysis and RIP assays. Finally, functional recovery assays and verified that SOX21-AS1 regulates the expression of EREG through combination with miR-451a and thus promotes the malignancy of PDAC. SOX21-AS1 was upregulated in PDAC. The upregulation of SOX21-AS1 can stimulate the proliferation, migration, invasion, stemness and epithelial-mesenchymal transition (EMT) progression of PDAC cells. Furthermore, PDAC cells secrete exosomal SOX21-AS1, which is absorbed by HUVECs and promotes angiogenesis. Our study first identified that SOX21-AS1 promotes the malignancy of PDAC through the SOX21-AS1/miR-451a/EREG axis, and also that exosomal SOX21-AS1 promotes angiogenesis in PDAC.

摘要

胰腺导管腺癌(PDAC)的发病率和死亡率有所上升。外泌体作为一种细胞间通讯的调节方式,含有长链非编码RNA(lncRNAs)。SOX21-AS1已在其他癌症中得到研究,其在PDAC中表达升高,但其在PDAC中的作用仍不清楚。首先,我们通过TCGA数据库分析了PDAC组织和非肿瘤组织中lncRNAs的表达。接下来,RT-qPCR实验结果证实了SOX21-AS1在PDAC组织中表达升高的预测。细胞功能实验证实,PDAC的恶性程度与SOX21-AS1的表达成正比。此外,通过外泌体分离和摄取实验,我们首次发现PDAC能够分泌外泌体SOX21-AS1,并在人脐静脉内皮细胞(HUVECs)中发挥促血管生成作用。随后,通过数据库预测分析和RNA免疫沉淀(RIP)实验验证了SOX21-AS1、miR-451a和表皮调节素(EREG)之间的关系。最后,功能恢复实验证实,SOX21-AS1通过与miR-451a结合来调节EREG的表达,从而促进PDAC的恶性进展。SOX21-AS1在PDAC中上调。SOX21-AS1的上调可刺激PDAC细胞的增殖、迁移、侵袭、干性和上皮-间质转化(EMT)进程。此外,PDAC细胞分泌外泌体SOX21-AS1,其被HUVECs吸收并促进血管生成。我们的研究首次确定SOX21-AS1通过SOX21-AS1/miR-451a/EREG轴促进PDAC的恶性进展,并且外泌体SOX21-AS1促进PDAC中的血管生成。

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