Zhang Tiequan, Li Mi, Lu Haofeng, Peng Tao
Department of Hepatobiliary Surgery, The First People's Hospital of Jingzhou, Jingzhou 434000, People's Republic of China.
Cancer Manag Res. 2021 Jan 12;13:247-258. doi: 10.2147/CMAR.S280307. eCollection 2021.
Accruing evidences have pointed out that abnormal expression of circular RNAs (circRNAs) was closely related to the development of many malignancies. The present study intended to disclose the role of circRNA eukaryotic translation initiation factor 6 (circEIF6; hsa_circ_0060055) in pancreatic cancer progression.
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circEIF6, messenger RNA (mRNA), microRNA-557 (miR-557) and solute carrier family 7 member 11 () mRNA. Cell proliferation ability, migration and invasion abilities and apoptosis were evaluated by Cell Counting Kit 8 (CCK8) assay, transwell migration and invasion assays and flow cytometry. Western blot assay was performed for the expression determination of all proteins. The predicted interaction between miR-557 and circEIF6 or was confirmed by dual-luciferase reporter assay. Xenograft tumor model was used for exploring the biological function of circEIF6 in vivo.
CircEIF6 abundance was aberrantly up-regulated in pancreatic tumor tissues and cell lines. Cell proliferation, migration and invasion were significantly restrained while cell apoptosis was induced with the silencing of circEIF6 in pancreatic cancer cells. CircEIF6 silencing also hampered the activation of phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway. CircEIF6 bound to miR-557, and circEIF6 silencing elevated the expression of miR-557 in pancreatic cancer cells. MiR-557 knockdown partly overturned circEIF6 silencing-induced effects in pancreatic cancer cells. was a target of miR-557, and miR-557 overexpression suppressed malignant potential of pancreatic cancer cells partly through reducing the expression of . CircEIF6 knockdown blocked xenograft tumor growth in vivo.
CircEIF6 aggravated pancreatic cancer development through promoting cell proliferation, migration and invasion and suppressing cell apoptosis through targeting miR-557//PI3K/AKT signaling.
越来越多的证据表明，环状RNA（circRNA）的异常表达与许多恶性肿瘤的发生发展密切相关。本研究旨在揭示环状RNA真核翻译起始因子6（circEIF6；hsa_circ_0060055）在胰腺癌进展中的作用。
采用定量实时聚合酶链反应（qRT-PCR）检测circEIF6、信使核糖核酸（mRNA）、微小RNA-557（miR-557）和溶质载体家族7成员11（）mRNA的表达。通过细胞计数试剂盒8（CCK8）检测、Transwell迁移和侵袭实验以及流式细胞术评估细胞增殖能力、迁移和侵袭能力以及细胞凋亡情况。采用蛋白质免疫印迹法检测所有蛋白质的表达。通过双荧光素酶报告基因实验证实miR-557与circEIF6或之间的预测相互作用。利用异种移植肿瘤模型在体内探索circEIF6的生物学功能。
circEIF6在胰腺癌组织和细胞系中异常上调。在胰腺癌细胞中，circEIF6沉默可显著抑制细胞增殖、迁移和侵袭，并诱导细胞凋亡。circEIF6沉默还阻碍了磷脂酰肌醇3激酶（PI3K）/AKT丝氨酸/苏氨酸激酶（AKT）通路的激活。circEIF6与miR-557结合，circEIF6沉默可提高胰腺癌细胞中miR-557的表达。miR-557敲低部分逆转了circEIF6沉默对胰腺癌细胞的影响。是miR-557的靶标，miR-557过表达部分通过降低的表达抑制胰腺癌细胞的恶性潜能。circEIF6敲低可阻断体内异种移植肿瘤的生长。
circEIF6通过靶向miR-557//PI3K/AKT信号通路促进细胞增殖、迁移和侵袭，抑制细胞凋亡，从而加重胰腺癌的发展。
