靶向miR-148b-5p可抑制免疫微环境和胃癌进展。
Targeting miR-148b-5p Inhibits Immunity Microenvironment and Gastric Cancer Progression.
作者信息
Zhang Yuyu, Huo Wei, Sun Lidi, Wu Jie, Zhang Chengbin, Wang Huanhuan, Wang Bin, Wei Jinlong, Qu Chao, Cao Hongshi, Jiang Xin
机构信息
Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.
Department of Pathology Oncology, The First Hospital of Jilin University, Changchun, China.
出版信息
Front Immunol. 2021 Feb 24;12:590447. doi: 10.3389/fimmu.2021.590447. eCollection 2021.
BACKGROUND
MicroRNAs (miRNAs) have been discovered to dictate the development of various tumors. However, studies on the roles of miRNAs in the progression of gastric cancer (GC) are still lacking.
METHODS
Herein, by analyzing GC cell lines and patients samples, we observed that miR-148b-5p was significantly downregulated in GC. We also confirmed that miR-148b-5p overexpression significantly inhibited GC cell proliferation and invasion and .
RESULTS
Overexpression of miR-148b-5p not only reprogrammed the metabolic properties of GC but also regulated the immune microenvironment by shifting lymphocyte and myeloid populations. Mechanistically, ATPIF1, an important glycolysis-associated gene, was identified as a direct target of miR-148b-5p and mediated the effect of miR-148b-5p. Notably, the low level of miR-148b-5p was significantly related with poor prognosis of GC patients ( < 0.001). Importantly, the levels of miR-148b-5p significantly changed the sensitivity of GC cells to several anti-cancer drugs (Doxorubicin, < 0.05, Paclitaxel, < 0.01, Docetaxel, < 0.05).
CONCLUSIONS
Targeting miR-148b-5p inhibits immunity microenvironment and gastric cancer progression.
背景
微小RNA（miRNA）已被发现可决定各种肿瘤的发展。然而，关于miRNA在胃癌（GC）进展中的作用的研究仍然缺乏。
方法
在此，通过分析GC细胞系和患者样本，我们观察到miR-148b-5p在GC中显著下调。我们还证实，miR-148b-5p的过表达显著抑制了GC细胞的增殖和侵袭。
结果
miR-148b-5p的过表达不仅重新编程了GC的代谢特性，还通过改变淋巴细胞和髓系细胞群体来调节免疫微环境。机制上，ATPIF1是一个重要的糖酵解相关基因，被确定为miR-148b-5p的直接靶点，并介导了miR-148b-5p的作用。值得注意的是，miR-148b-5p的低水平与GC患者的不良预后显著相关（<0.001）。重要的是，miR-148b-5p的水平显著改变了GC细胞对几种抗癌药物的敏感性（阿霉素，<0.05；紫杉醇，<0.01；多西他赛，<0.05）。
结论
靶向miR-148b-5p可抑制免疫微环境和胃癌进展。
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