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Targeting miR-148b-5p Inhibits Immunity Microenvironment and Gastric Cancer Progression.

Frontiers in immunology (2021-03-16)
Yuyu Zhang, Wei Huo, Lidi Sun, Jie Wu, Chengbin Zhang, Huanhuan Wang, Bin Wang, Jinlong Wei, Chao Qu, Hongshi Cao, Xin Jiang
ABSTRACT

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. 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 in vitro and in vivo. 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 (P < 0.001). Importantly, the levels of miR-148b-5p significantly changed the sensitivity of GC cells to several anti-cancer drugs (Doxorubicin, P < 0.05, Paclitaxel, P < 0.01, Docetaxel, P < 0.05). Targeting miR-148b-5p inhibits immunity microenvironment and gastric cancer progression.

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MISSION® esiRNA, targeting human ATPIF1