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微小RNA-374b通过下调细胞因子诱导的杀伤细胞上程序性细胞死亡蛋白1的表达来抑制肝癌进展。

MicroRNA-374b inhibits liver cancer progression via down regulating programmed cell death-1 expression on cytokine-induced killer cells.

作者信息

Huang Fen, Wang Bo, Zeng Jiangzheng, Sang Shenggang, Lei Junhua, Lu Yanda

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.

Department of Emergency, Hainan General Hospital, Haikou, Hainan 570311, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):4797-4804. doi: 10.3892/ol.2018.7951. Epub 2018 Feb 5.

Abstract

Programmed cell death-1 (PD-1) is an oncogene associated with suppressing proliferation and cytokine production of T cells in the progression of liver cancer. microRNAs (miRs) regulate gene expression via specific binding to the target 3'untranslated region of mRNA. In the present study, miR-374b was indicated to interact with PD-1 and affect the tumor-targeting capacity of cytokine-induced killer (CIK) cells. miR-374b inhibitor significantly increased PD-1 expression in CIK cells. A synthetic small interfering (si)RNA targeting PD-1 was employed to silence the expression level of PD-1 in CIK cells. Then, the antitumor effect of siPD-1 in CIK cells was investigated. study demonstrated that IFN-γ secretion and the concentration of lactate dehydrogenase were significantly increased in the PD-1 knockdown group; however, the viability of HepG2 cells in the PD-1 knockdown group had significantly decreased, compared with the HepG2 cells in the negative control group. study indicated that mice inoculated with HepG2 cells and CIK cells with PD-1 knocked down had a significantly smaller tumor volume, compared with the control group. To conclude, human CIK cells transfected with siPD-1 can target liver cancer cells and enhance immunotherapy efficacy, and therefore they have potential in the immunotherapy of liver cancer.

摘要

程序性细胞死亡蛋白1(PD-1)是一种癌基因,在肝癌进展过程中与抑制T细胞增殖和细胞因子产生有关。微小RNA(miR)通过特异性结合mRNA的靶标3'非翻译区来调节基因表达。在本研究中,miR-374b被表明与PD-1相互作用,并影响细胞因子诱导的杀伤(CIK)细胞的肿瘤靶向能力。miR-374b抑制剂显著增加了CIK细胞中PD-1的表达。使用一种靶向PD-1的合成小干扰(si)RNA来沉默CIK细胞中PD-1的表达水平。然后,研究了siPD-1在CIK细胞中的抗肿瘤作用。研究表明,PD-1敲低组中γ干扰素分泌和乳酸脱氢酶浓度显著增加;然而,与阴性对照组中的HepG2细胞相比,PD-1敲低组中HepG2细胞的活力显著降低。研究表明,接种了敲低PD-1的HepG2细胞和CIK细胞的小鼠的肿瘤体积明显小于对照组。总之,用siPD-1转染的人CIK细胞可以靶向肝癌细胞并增强免疫治疗效果,因此它们在肝癌免疫治疗中具有潜力。

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