Long non-coding RNAs (lncRNAs) 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-MDSCs) remains unclear. Here, we identified that the lncRNA AK036396 was highly expressed in PMN-MDSCs, and lncRNA AK036396 knockdown 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 lncRNA AK036396, based on microarray results. LncRNA AK036396 knockdown 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 lncRNA AK036396 can inhibit maturation and accelerate immunosuppression of PMN-MDSCs by enhancing Fcnb protein stability.

中文翻译：

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LncRNA AK036396通过增强Ficolin B的稳定性来抑制成熟并加速多形核髓样抑制细胞的免疫抑制。

长的非编码RNA（lncRNA）逐渐成为细胞生物学的重要调节剂。但是，lncRNAs在多形核髓样抑制细胞（PMN-MDSCs）的发育和功能中的作用尚不清楚。在这里，我们确定了lncRNA AK036396在PMN-MDSCs中高表达，而lncRNA AK036396的敲低促进了成熟并降低了PMN-MDSCs的抑制功能。根据微阵列结果，Ficolin B（Fcnb）的表达可以作为PMN-MDSC发育的替代物，是lncRNA AK036396的预测靶基因。LncRNA AK036396敲低以依赖泛素-蛋白酶体系统的方式减弱了Fcnb蛋白的稳定性。此外，Fcnb抑制下调了PMN-MDSCs的抑制功能。此外，人类M-纤维胶蛋白的表达 它是小鼠Fcnb的直系同源基因，与精氨酸酶1（ARG1）表达呈正相关。该抑制分子由MDSCs释放，其产生通常用于代表MDSCs在肺癌患者中的抑制活性，表明这些发现在临床上具有相关性。这些结果表明，lncRNA AK036396可通过增强Fcnb蛋白的稳定性来抑制成熟并加速PMN-MDSC的免疫抑制。