Department of Clinical Laboratory, The 89th Hospital of The People's Liberation Army, Weifang, Shandong, China.
National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
Cancer Biomark. 2020;27(4):471-484. doi: 10.3233/CBM-190314.
Gastric cancer is one of the leading causes of death worldwide. MicroRNA-30a (miR-30a) has been demonstrated to be involved in several types of cancer development.
We aimed to identify the molecular mechanism of miR-30a in gastric cancer.
We investigated the expression of miR-30a in gastric cancer tissues by qRT-PCR. The role of miR-30a on the metastasis and proliferation of gastric cancer was evaluated by cell migration assay, CCK-8 assay and tumor peritoneal dissemination model. The target of miR-30a in gastric cancer was identified.
We discovered that miR-30a was significantly downregulated in gastric cancer tissues compared with adjacent nonmalignant tissues. The expression of miR-30a was inversely correlated with progression of gastric cancer. Gain- and loss-of function revealed that miR-30a acted as a potent tumor suppressor in gastric cancer. Re-expressed miR-30a inhibited gastric cancer cells migration, knock down miR-30a have the opposite effects. Furthermore, overexpression of miR-30a suppressed tumor peritoneal dissemination in vivo. We identified that fibroblast activation protein α (FAPα) was a direct target of miR-30a. The relative expression of FAPα was significantly higher in gastric cancer tissues compared with adjacent nonmalignant tissues. Inhibition of FAPα could recapitulate the effects of miR-30a, and overexpression of FAPα could abrogate the effect of miR-30a.
MiR-30a inhibited gastric cancer metastasis by targeting FAPα, suggesting that miR-30a may function as a novel tumor suppressor in gastric cancer.
胃癌是全球主要的死亡原因之一。MicroRNA-30a (miR-30a) 已被证明参与了多种类型的癌症发展。
我们旨在确定 miR-30a 在胃癌中的分子机制。
我们通过 qRT-PCR 检测了胃癌组织中 miR-30a 的表达。通过细胞迁移实验、CCK-8 实验和肿瘤腹膜扩散模型评估了 miR-30a 对胃癌转移和增殖的作用。鉴定了 miR-30a 在胃癌中的靶基因。
我们发现 miR-30a 在胃癌组织中的表达明显低于相邻的非恶性组织。miR-30a 的表达与胃癌的进展呈负相关。功能获得和功能丧失实验表明,miR-30a 在胃癌中作为一种有效的肿瘤抑制因子发挥作用。重新表达 miR-30a 抑制了胃癌细胞的迁移,而敲低 miR-30a 则产生相反的效果。此外,过表达 miR-30a 抑制了体内肿瘤腹膜扩散。我们鉴定出成纤维细胞激活蛋白α (FAPα) 是 miR-30a 的直接靶基因。FAPα 的相对表达在胃癌组织中明显高于相邻的非恶性组织。抑制 FAPα 可以再现 miR-30a 的作用,而过表达 FAPα 可以消除 miR-30a 的作用。
miR-30a 通过靶向 FAPα 抑制胃癌转移,提示 miR-30a 可能在胃癌中作为一种新的肿瘤抑制因子发挥作用。