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miR-365 的上调通过抑制 PAX6 抑制胃癌细胞的恶性行为。

Elevation of microRNA-365 impedes malignant behaviors of gastric cancer cells by inhibiting PAX6.

机构信息

Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, No. 648 Dongfeng East Road, Lianchi District, Baoding 071000, Hebei, People's Republic of China.

Pharmacy Department, Baoding NO. 2 Central Hospital, Baoding, Hebei, China.

出版信息

Funct Integr Genomics. 2022 Oct;22(5):825-834. doi: 10.1007/s10142-022-00858-4. Epub 2022 Apr 28.

Abstract

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

摘要

微小 RNA-365(miR-365)已被证实是多种癌症发生肿瘤的重要调节因子,而关于 miR-365 表达与胃癌(GC)的知识存在很大差距。本研究聚焦于 miR-365 和配对盒基因 6(PAX6)对 GC 发展的影响。测定 GC 组织和细胞系中 miR-365 和 PAX6 的水平,然后筛选 AGS 和 NCI-N87 细胞。通过增益或缺失功能测定来分析 miR-365、PAX6 对 AGS 和 NCI-N87 细胞行为的影响。观察改变的 miR-365 和 PAX6 对动物模型的影响。此外,为了评估 miR-365 和 PAX6 之间的相互作用,我们采用了生物信息学方法和双荧光素酶报告基因检测。GC 组织和细胞系中 miR-365 降低而 PAX6 升高。miR-365 和 PAX6 之间存在负相关。上调的 miR-365 可以抑制体内 GC 的致癌性和体外恶性转化。PAX6 是 miR-365 的靶基因。过表达 PAX6 逆转了上调 miR-365 对胃癌细胞恶性行为的抑制作用。我们的研究表明,miR-365 的扩增可以通过抑制 PAX6 抑制 GC 细胞的恶性行为,这可能有助于 GC 的治疗。

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