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(人源环状RNA分子hsa_circ_0000919)通过 轴促进胰腺导管腺癌的细胞增殖和转移并抑制细胞凋亡:对新型治疗靶点的启示

(hsa_circ_0000919) promotes cell proliferation and metastasis and inhibits cell apoptosis in pancreatic ductal adenocarcinoma via the axis: implications for novel therapeutic targets.

作者信息

Wangpu Xiongzhi, Zhao Jingkun, Yu Chaoran, Yu Song, Wang Hongcheng, Yuan Zhou, Huang Xinyu

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Shanghai 6th People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine No. 600 Yishan Rd, Shanghai 200233, China.

Department of Gastrointestinal Surgery and Minimally Invasive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai 200001, China.

出版信息

Am J Cancer Res. 2023 Nov 15;13(11):5610-5625. eCollection 2023.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously aggressive malignancy with a survival rate of merely 9%. The prognosis in patients with PDAC is relatively poor, particularly in patients with advanced distant metastases. However, the mechanisms of PDAC progression remain elusive. Circular RNAs (circRNAs) have been implicated in the development of various malignancies, including PDAC. Therefore, this study aimed to investigate how a novel circRNA, , regulates PDAC progression. We used the GEO database to determine expression levels in cancer and adjacent cells and employed the limma package of R software to identify differentially expressed circRNAs. We detected the expression of , , and using qRT-PCR and investigated the effect of on cell proliferation, migration, invasion, and apoptosis using the Cell Counting Kit-8 (CCK-8), the transwell migration assay, and the flow cytometry assay. We then performed RNA pull-down assay, RNA immunoprecipitation (RIP), and Western blot to verify the interaction between , , , and . Moreover, we used a naked mice model to determine how affects tumor growth and progression . Loss and gain of function analyses revealed that upregulation promotes cell proliferation, migration, invasion and tumor growth both and , which results in PDAC progression and poor prognosis in patients. knockdown significantly impaired cell proliferation and migration of PDAC cell lines. Additionally, knockdown significantly increased the expression of and , while reducing the expression of ( < 0.05), indicating that and are downstream targets of . Rescue experiments support the interactions between , , , and . In conclusion, we demonstrated that sponges the /axis, acting as an oncogene to promote PDAC development.

摘要

胰腺导管腺癌(PDAC)是一种侵袭性极强的恶性肿瘤,生存率仅为9%。PDAC患者的预后相对较差,尤其是晚期远处转移患者。然而,PDAC进展的机制仍不清楚。环状RNA(circRNAs)已被证明与包括PDAC在内的各种恶性肿瘤的发生发展有关。因此,本研究旨在探讨一种新型环状RNA, ,如何调节PDAC的进展。我们使用GEO数据库确定癌症和相邻细胞中的 表达水平,并使用R软件的limma包来识别差异表达的circRNAs。我们使用qRT-PCR检测 、 和 的表达,并使用细胞计数试剂盒-8(CCK-8)、transwell迁移试验和流式细胞术试验研究 对细胞增殖、迁移、侵袭和凋亡的影响。然后,我们进行了RNA下拉试验、RNA免疫沉淀(RIP)和蛋白质免疫印迹,以验证 、 、 和 之间的相互作用。此外,我们使用裸鼠模型来确定 如何影响肿瘤生长和进展。功能缺失和获得分析表明, 上调促进 和 中的细胞增殖、迁移、侵袭和肿瘤生长,这导致PDAC进展和患者预后不良。 敲低显著损害了PDAC细胞系的细胞增殖和迁移。此外, 敲低显著增加了 和 的表达,同时降低了 的表达( < 0.05),表明 和 是 的下游靶点。挽救实验支持了 、 、 和 之间的相互作用。总之,我们证明 可吸附 /轴,作为一种癌基因促进PDAC的发展。

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本文引用的文献

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Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis.
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