Department of General Surgery, Fourth Affiliated Hospital of Anhui Medical University, Hefei 230012, China.
Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Jan 2;52(1):49-57. doi: 10.1093/abbs/gmz141.
Gastric cancer (GC) is one of malignant tumors with high mortality and morbidity in the world. MicroRNA-122 (miR-122) acts as a tumor suppressor in a variety of cancers and has been found to be dominant in gastric adenocarcinoma. However, the specific biological function of miR-122-5p in GC is not completely clear. In this study, we found that miR-122-5p was low-expressed in GC tissues and cell lines by using qRT-PCR. Overexpression of miR-122-5p inhibited the proliferation, migration, and invasion of GC cells by using CCK-8 and transwell assays. On the contrary, downregulation of miR-122-5p promoted the proliferation, migration, and invasion of GC cells. In addition, we found that the expression of LYN, an Src family tyrosine kinase, was inversely correlated with miR-122-5p expression in GC tissues by using western blot analysis, immunohistochemistry, and qRT-PCR assays. Meanwhile, luciferase assay results indicated that LYN is a direct target of miR-122-5p in GC cells. Moreover, silencing LYN expression by its siRNA inhibited the proliferation, migration, and invasion of GC cells. Importantly, overexpression of LYN restored miR-122-5p-mediated inhibition of the proliferation, migration, and invasion of GC cells. Taken together, our results indicated miR-122-5p inhibited the proliferation, migration, and invasion by targeting LYN in GC.
胃癌（GC）是世界上死亡率和发病率较高的恶性肿瘤之一。MicroRNA-122（miR-122）在多种癌症中作为肿瘤抑制因子发挥作用，并且已被发现在胃腺癌中占主导地位。然而，miR-122-5p 在 GC 中的具体生物学功能尚不完全清楚。在本研究中，我们通过 qRT-PCR 发现 miR-122-5p 在 GC 组织和细胞系中低表达。通过 CCK-8 和 Transwell 实验发现，过表达 miR-122-5p 抑制了 GC 细胞的增殖、迁移和侵袭。相反，下调 miR-122-5p 促进了 GC 细胞的增殖、迁移和侵袭。此外，我们通过 Western blot 分析、免疫组化和 qRT-PCR 实验发现，在 GC 组织中，原癌基因 Lyn，一种Src 家族酪氨酸激酶的表达与 miR-122-5p 的表达呈负相关。同时，荧光素酶报告基因实验结果表明，Lyn 是 GC 细胞中 miR-122-5p 的直接靶基因。此外，通过其 siRNA 沉默 Lyn 表达抑制了 GC 细胞的增殖、迁移和侵袭。重要的是，过表达 Lyn 恢复了 miR-122-5p 介导的对 GC 细胞增殖、迁移和侵袭的抑制作用。综上所述，我们的研究结果表明，miR-122-5p 通过靶向 LYN 抑制 GC 细胞的增殖、迁移和侵袭。
