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miRNA-222-3p 促进肿瘤细胞迁移和侵袭,抑制细胞凋亡,并与肾细胞癌患者的不良预后相关。

MicroRNA‑222‑3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with an unfavorable prognosis of patients with renal cell carcinoma.

机构信息

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.

Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.

出版信息

Int J Mol Med. 2019 Jan;43(1):525-534. doi: 10.3892/ijmm.2018.3931. Epub 2018 Oct 15.

DOI:10.3892/ijmm.2018.3931
PMID:30320376
Abstract

The aim of the present study was to investigate the role of microRNA (miR)‑222‑3p in renal cell carcinoma (RCC). The expression level of miR‑222‑3p was detected in RCC tissues and cell lines (ACHN, 786‑O, Caki‑1 and 769‑P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK‑2 cells. Further in vitro experiments demonstrated that the over-expression of miR‑222‑3p promoted the migration and invasion, and attenuated the apoptosis of 786‑O cells, whereas the knockdown of miR‑222‑3p suppressed the migration and invasion and induced the apoptosis of 786‑O cells. Similar results were observed in the ACHN cell line in terms of migration, invasion and apoptosis. Furthermore, the expression level of miR‑222‑3p was measured in 42 RCC formaldehyde‑fixed paraffin‑embedded samples, and the association between the expression of miR‑222‑3p and the pathological characteristics and overall survival rate of patients with RCC was analyzed. The results demonstrated that patients with a higher expression of miR‑222‑3p had a significantly lower overall survival rate, compared with those with a lower expression of miR‑222‑3p [hazard ratio (HR)=5.120; P=0.036]. Multivariate analysis identified that patients with a higher expression of miR‑222‑3p retained the statistically significant decrease in overall survival rate compared with patients with a lower expression of miR‑222‑3p (HR=5.636; P=0.030). Furthermore, Kaplan‑Meier survival curves indicated that patients with higher miR‑222‑3p had significantly lower overall survival rates compared with patients with lower miR‑222‑3p (P=0.020). Taken together, these results suggested that miR‑222‑3p serves as an onco‑miR in RCC and may be a potential prognostic biomarker and therapeutic target in patients with RCC.

摘要

本研究旨在探讨微小 RNA(miR)-222-3p 在肾细胞癌(RCC)中的作用。检测了 miR-222-3p 在 RCC 组织和细胞系(ACHN、786-O、Caki-1 和 769-P)中的表达水平,与相邻正常肾组织和 HK-2 细胞相比,其表达水平明显上调。进一步的体外实验表明,miR-222-3p 的过表达促进了 786-O 细胞的迁移和侵袭,并减弱了其凋亡,而 miR-222-3p 的敲低则抑制了 786-O 细胞的迁移和侵袭,并诱导了其凋亡。在 ACHN 细胞系中,迁移、侵袭和凋亡也观察到了类似的结果。此外,还测量了 42 例 RCC 福尔马林固定石蜡包埋样本中 miR-222-3p 的表达水平,并分析了 miR-222-3p 的表达与 RCC 患者的病理特征和总生存率之间的关系。结果表明,miR-222-3p 表达较高的患者总生存率明显低于 miR-222-3p 表达较低的患者[风险比(HR)=5.120;P=0.036]。多变量分析表明,与 miR-222-3p 表达较低的患者相比,miR-222-3p 表达较高的患者总生存率明显下降(HR=5.636;P=0.030)。此外,Kaplan-Meier 生存曲线表明,miR-222-3p 较高的患者总生存率明显低于 miR-222-3p 较低的患者(P=0.020)。综上所述,这些结果表明,miR-222-3p 是 RCC 的致癌 miRNA,可能是 RCC 患者潜在的预后生物标志物和治疗靶点。

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