LncRNA AK036396 Inhibits Maturation and Accelerates Immunosuppression of Polymorphonuclear Myeloid-Derived Suppressor Cells by Enhancing the Stability of Ficolin B
LncRNA AK036396 Inhibits Maturation and Accelerates Immunosuppression of Polymorphonuclear Myeloid-Derived Suppressor Cells by Enhancing the Stability of Ficolin B
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LncRNA AK036396 通过增强 Ficolin B 的稳定性来抑制多形核骨髓源性抑制细胞的成熟并加速免疫抑制
DOI：
10.1158/2326-6066.cir-19-0595
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发表时间：
2020-04-01
影响因子：
10.1
通讯作者：
Wang，Shengjun
中科院分区：
文献类型：
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作者：
Tian，Xinyu;Zheng，Yu;Wang，Shengjun
长非编码RNA(LncRNA)正在成为细胞生物学的重要调节因子。然而，LncRNAs在多形核髓系来源的抑制细胞(PMN-MDSC)的发育和功能中的作用仍不清楚。在此，我们证实了lncRNAF730016J06Rik(AK036396)在PMN-MDSCs中高表达，并且lncRNAAK036396基因敲除促进了PMN-MDSCs的成熟，降低了其抑制功能。Fcnb是基因芯片结果预测的LncRNAAK036396的靶基因，其表达水平可作为PMN-MDSC发育的替代基因。LncRNAAK036396基因敲除使Fcnb蛋白的稳定性减弱，这种作用依赖于泛素-蛋白酶体系统。此外，Fcnb抑制可下调PMN-MDSCs的抑制功能。此外，与小鼠Fcnb同源的人M-无花果蛋白的表达增加，并与精氨酸酶1(ARG1)的表达呈正相关。这种抑制分子是由MDSCs释放的，它的产生通常用于代表肺癌患者MDSCs的抑制活性，提示这些发现与临床相关。这些结果表明，lncRNAAK036396可通过提高Fcnb蛋白的稳定性来抑制PMN-MDSCs的成熟，促进其免疫抑制。
Long noncoding RNAs (lncRNA) are emerging as crucial regulators of cell biology. However, the role of lncRNAs in the development and function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) remains unclear. Here, we identified that the lncRNAF730016J06Rik (AK036396)was highly expressed in PMN-MDSCs and that lncRNAAK036396knockdown promoted the maturation and decreased the suppressive function of PMN-MDSCs. Ficolin B (Fcnb), the expression of which could be assessed as a surrogate for PMN-MDSC development, was the predicted target gene of lncRNAAK036396based on microarray results. LncRNAAK036396knockdown attenuated Fcnb protein stability in a manner dependent on the ubiquitin-proteasome system. Moreover, Fcnb inhibition downregulated the suppressive function of PMN-MDSCs. In addition, the expression of human M-ficolin, which is an ortholog of mouse Fcnb, was increased and positively correlated with arginase1 (ARG1) expression. This suppressive molecule is released by MDSCs, and its production is commonly used to represent the suppressive activity of MDSCs in patients with lung cancer, suggesting clinical relevance for these findings. These results indicate that lncRNAAK036396can inhibit maturation and accelerate immunosuppression of PMN-MDSCs by enhancing Fcnb protein stability.