Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, 1 Xianglong Road, Dongguan City, 510080, Guangdong Province, China.
Department of Clinical Pharmacy, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan City, China.
Dig Dis Sci. 2021 Aug;66(8):2637-2650. doi: 10.1007/s10620-020-06581-z. Epub 2020 Sep 10.
Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC).
The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells.
We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression.
Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
长链非编码 RNA 作为竞争性内源性 RNA（ceRNA）网络的关键组成部分，参与肿瘤的发生。我们研究了 lncRNA FAM230B 在胃癌（GC）中的致病作用及其分子机制。
通过实时定量 RT-PCR 比较 FAM230B 在五种胃癌细胞系和人胃黏膜细胞中的表达水平。为了分析 FAM230B 在 GC 中的功能，我们在 AGS 细胞中过表达 FAM230B，在 MGC-803 细胞中沉默 FAM230B，并在裸鼠中检测 FAM230B 对肿瘤生长的影响。通过生物信息学分析预测 miR-27a-5p 与 FAM230B 之间的相互作用，并用双荧光素酶报告基因实验进行验证。我们还通过在 MGC-803 胃癌细胞中强制过表达 miR-27a-5p，进一步研究 FAM230B 的作用和机制。
我们发现 FAM230B 在胃癌细胞系中高表达，主要位于细胞质中。FAM230B 过表达促进 AGS 细胞的增殖、迁移和侵袭，并抑制其凋亡；同时促进体内肿瘤生长。相反，FAM230B 敲低抑制 MGC0803 细胞的增殖、迁移和侵袭，但增强其凋亡并抑制体内肿瘤生长。FAM230B 过表达可抑制 AGS 细胞中 miR-27a-5p 的表达。miR-27a-5p 通过降低 TOP2A（拓扑异构酶 2α）表达抑制胃癌细胞的增殖、迁移和侵袭，并促进胃癌细胞的凋亡。
我们的研究表明，lncRNA FAM230B 可能促进 GC 的发生。FAM230B 通过海绵吸附 miR-27a-5p 并增强 TOP2A 表达，作为 ceRNA 发挥作用。
