KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation
KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation
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KIR2DL4 促进与 PI3K/Akt 信号激活相关的 RCC 细胞增殖
DOI：
10.1016/j.lfs.2022.120320
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发表时间：
2022-01-19
期刊：
影响因子：
6.1
通讯作者：
Chen, Guang
中科院分区：
文献类型：
--
作者：
Ding, Xiao-Fei;Chen, Jie;Chen, Guang
背景资料：杀伤细胞免疫球蛋白样受体2DL 4（KIR 2DL 4）是一种跨膜糖蛋白，由自然杀伤（NK）细胞和某些T细胞亚群表达。方法：本研究采用生物信息学分析、免疫组化、免疫印迹、MTT细胞活力测定、软琼脂集落形成测定和裸鼠人肾细胞癌（RCC）移植瘤模型，检测KIR 2DL 4在RCC中的表达及其在RCC进展中的作用。我们证实KIR 2DL 4在RCC细胞中过表达。MTT和软琼脂克隆分析显示，KIR 2DL 4敲低延迟RCC细胞系Caki-1和769-P的细胞增殖和活力。相比之下，KIR 2DL 4过表达在体外和体内均促进Caki-1细胞增殖，这在BALB/c-nu/nu异种移植小鼠模型中观察到。此外，RNA测序数据表明，在平行对照和过表达KIR 2DL 4的Caki-1细胞之间发现的差异表达基因与癌症发展高度相关，其中与磷脂酰肌醇-3-激酶（PI 3 K）/蛋白激酶B（AKT）信号通路相关的基因特别富集，免疫印迹数据显示，与平行对照细胞相比，KIR 2DL 4过表达或KIR 2DL 4敲低的Caki-1细胞中的AKT磷酸化水平更高或更低。此外，PI 3 K抑制剂wortmannin处理和KIR 2DL 4-shRNA转染进一步下调磷酸化AKT水平和Caki-1细胞增殖。结论：我们的研究结果表明，KIR 2DL 4也在RCC细胞中表达，这促进了与PI 3 K/AKT激活相关的RCC进展。
Background: Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. However, its expression profiles and functions in solid tumor progression remain poorly defined.Methods: In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT cell viability assay, soft agar colony formation assay and a human renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression.Results: We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation and viability in RCC cell lines, Caki-1 and 769-P, in vitro. By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes found between parallel-controlled and Caki-1 cells overexpressing KIR2DL4 were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were particularly enriched, immunoblotting data showed that the level of AKT phosphorylation was higher or lower in KIR2DL4 overexpressing or KIR2DL4 knocking-down Caki-1 cells compared with that in the parallel-controlled cells. In addition, PI3K inhibitor wortmannin treatment and KIR2DL4-shRNA transfection further deregulated the levels of phosphorylated AKT and Caki-1 cell proliferation.Conclusions: Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression associated with PI3K/AKT activation.