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微小RNA-552通过靶向叉头框蛋白O1促进肝内胆管癌的增殖和转移。

miR-552 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma by targeting FOXO1.

作者信息

Cheng Zhangjun, Cheng Nuo, Tang Xuewu, Yang Facai, Ma Weihu, Yu Qiushi, Tang Haolan, Xiao Qianru, Lei Zhengqing

机构信息

Department of Hepato-Pancreato-Biliary Centers, Zhong Da Hospital, School of Medicine, Southeast University, 210009, Nanjing, China.

School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Exp Cell Res. 2023 Oct 1;431(1):113741. doi: 10.1016/j.yexcr.2023.113741. Epub 2023 Aug 5.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly malignant cancer. Few effective systemic targeted therapies are available for patients with unresectable ICC, but there exists an urgent need to explore mechanisms underlying the initiation and progression of ICC. MicroRNA (miRNA) plays vital roles in the initiation, progression, and drug resistance of different cancers. Recently, the biological function of a novel miRNA, miR-552, has been widely analyzed in hepatocellular carcinoma and colorectal, cervical, gastric, and other cancers. However, its role in ICC has not yet been elucidated. In this study, we found that miR-552 expression was upregulated in ICC and that miR-552 predicted poor prognosis. Using functional studies, we found that miR-552 enhanced the proliferation and invasion ability of ICC cells. Mechanistic research identified that forkhead box O1 (FOXO1) is the target of miR-552 in ICC. Moreover, the combined panels of miR-552 and FOXO1 exhibited a better prognostic value for ICC patients than did miR-552 alone. In conclusion, these findings demonstrated that the miR-552/FOXO1 axis drove ICC progression, further suggesting that targeting this axis could be a novel therapeutic strategy for ICC.

摘要

肝内胆管癌(ICC)是一种相对罕见但恶性程度很高的癌症。对于不可切除的ICC患者,几乎没有有效的全身靶向治疗方法,但迫切需要探索ICC发生和发展的潜在机制。微小RNA(miRNA)在不同癌症的发生、发展和耐药性中起着至关重要的作用。最近,一种新型miRNA——miR-552的生物学功能已在肝细胞癌、结直肠癌、宫颈癌、胃癌及其他癌症中得到广泛分析。然而,其在ICC中的作用尚未阐明。在本研究中,我们发现miR-552在ICC中表达上调,且miR-552预示着预后不良。通过功能研究,我们发现miR-552增强了ICC细胞的增殖和侵袭能力。机制研究确定叉头框O1(FOXO1)是ICC中miR-552的靶标。此外,与单独的miR-552相比,miR-组合对ICC患者具有更好的预后价值。总之,这些发现表明miR-552/FOXO1轴推动了ICC的进展,进一步表明靶向该轴可能是ICC的一种新型治疗策略。

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