Department of General Surgery, Huai'an Second People's Hospital and the Affiliated Huai'an Hospital of Xuzhou Medical University, 62 Huaihai South Road, Huai'an, Jiangsu 223001, PR China.
J Biochem. 2020 Nov 1;168(5):547-555. doi: 10.1093/jb/mvaa079.
MiR-301a is as an oncogene involved in the regulation of gastric cancer (GC) progression, but the underlying mechanism is unclear. This study was to explore the lncRNA PCAT18/miR-301a/TP53INP1 axis in regulating the GC cell proliferation and metastasis. In the present study, GC tissues and cell lines were collected for the detection of PCAT18 expression. Herein, we found that PCAT18 is significantly decreases in human GC tissues and five GC cell lines. Overexpression of PCAT18 inhibits cell viability, invasion and migration of GC cells and tumour growth of GC xenograft tumours. PCAT18 negatively regulates the expression level of miR-301a. The interaction between PCAT18 and miR-301a is confirmed by RIP and RNA pull down. MiR-301a mimic increases cell viability and promotes cell migration and invasion and reverses the inhibitory action of PCAT18. TP53INP1 expression is negatively regulated by miR-301a and TP53INP1/miR-301a is involved in GC viability, migration and invasion. The promoting of PCAT18 on TP53INP1 expression is abolished by miR-301a overexpression. In conclusion, lncRNA PCAT18 acts as a tumour suppressor for GC and lncRNA PCAT18, miR-301a and TP53INP1 comprise a signal axis in regulating GC cell proliferation, migration and invasion.
miR-301a 作为一种癌基因，参与调控胃癌（GC）的进展，但具体机制尚不清楚。本研究旨在探讨 lncRNA PCAT18/miR-301a/TP53INP1 轴在调控 GC 细胞增殖和转移中的作用。在本研究中，收集 GC 组织和细胞系检测 PCAT18 的表达。结果发现，PCAT18 在人 GC 组织和 5 种 GC 细胞系中表达明显下调。过表达 PCAT18 可抑制 GC 细胞的活力、侵袭和迁移以及 GC 异种移植瘤的生长。PCAT18 负调控 miR-301a 的表达水平。PCAT18 和 miR-301a 之间的相互作用通过 RIP 和 RNA 下拉实验得到证实。miR-301a 模拟物可增加细胞活力，促进细胞迁移和侵袭，并逆转 PCAT18 的抑制作用。TP53INP1 的表达受 miR-301a 的负调控，TP53INP1/miR-301a 参与 GC 的活力、迁移和侵袭。miR-301a 过表达可消除 PCAT18 对 TP53INP1 表达的促进作用。综上所述，lncRNA PCAT18 作为 GC 的肿瘤抑制因子，lncRNA PCAT18、miR-301a 和 TP53INP1 构成了调控 GC 细胞增殖、迁移和侵袭的信号轴。
