Golgi membrane protein 1 (GOLM1/GP73) is a serum marker of hepatocellular carcinoma (HCC). We have previously shown that mTOR promoted tumorigenesis of HCC through stimulating GOLM1 expression. In this study, we demonstrated that the mammalian target of rapamycin (mTOR) was a negative regulator of microRNA-145 (miR-145) expression. miR-145 inhibited GOLM1 expression by targeting a coding sequence of GOLM1 gene. GOLM1 and miR-145 were inversely correlated in human HCC tissues. GOLM1-enriched exosomes activated the glycogen synthase kinase-3β/matrix metalloproteinases (GSK-3β/MMPs) signaling axis of recipient cells and accelerated cell proliferation and migration. In contrast, miR-145 suppressed tumorigenesis and metastasis. We suggest that mTOR/miR-145/GOLM1 signaling pathway should be targeted for HCC treatment.

高尔基体膜蛋白1（GOLM1 / GP73）是肝细胞癌（HCC）的血清标志物。先前我们已经表明，mTOR通过刺激GOLM1表达促进了肝癌的发生。在这项研究中，我们证明了雷帕霉素（mTOR）的哺乳动物靶标是microRNA-145（miR-145）表达的负调节剂。miR-145通过靶向GOLM1基因的编码序列来抑制GOLM1表达。GOLM1和miR-145在人类HCC组织中呈负相关。富含GOLM1的外泌体激活了受体细胞的糖原合酶激酶3β/基质金属蛋白酶（GSK-3β/ MMPs）信号轴，并加速了细胞的增殖和迁移。相比之下，miR-145抑制肿瘤发生和转移。我们建议mTOR / miR-145 / GOLM1信号通路应作为HCC治疗的靶标。