Departments of Gastroenterology, The Second Xiangya Hospital of Central South University, No. 139 RenMin Road, Changsha, 410011, Hunan, China.
Biol Res. 2020 Apr 15;53(1):14. doi: 10.1186/s40659-020-00283-6.
Previous studies have shown that long noncoding RNA (lncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this lncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1).
Thirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo.
LINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis.
Knockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR-490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.
先前的研究表明，长链非编码 RNA（lncRNA）LINC00483 在包括胃癌在内的人类癌症中表达异常。然而，这种 lncRNA 在胃癌中的调控机制在很大程度上仍然未知。本研究旨在探讨 LINC00483 对胃癌发展的影响，并探索 LINC00483/微小 RNA（miR）-490-3p/丝裂原活化蛋白激酶 1（MAPK1）的潜在调控网络。
招募 30 名胃癌患者进行组织采集。通过定量实时聚合酶链反应或 Western blot 检测 LINC00483、miR-490-3p 和 MAPK1 的表达水平。通过 MTT、流式细胞术、Transwell 测定和 Western blot 分别测定细胞活力、凋亡、迁移和侵袭。通过荧光素酶报告实验证实 miR-490-3p 与 LINC00483 或 MAPK1 之间的靶标关联。建立异种移植模型以评估 LINC00483 在体内的功能。
LINC00483 和 MAPK1 水平在胃癌组织和细胞中升高。敲低 LINC00483 或 MAPK1 抑制胃癌细胞的活力、迁移和侵袭，但促进细胞凋亡。此外，MAPK1 的过表达减弱了 LINC00483 敲低对胃癌发展的影响。LINC00483 通过竞争性地吸附 miR-490-3p 来增加 MAPK1 的表达。miR-490-3p 的过表达抑制了胃癌的发展，而引入 LINC00483 则减轻了这种抑制作用。此外，抑制 LINC00483 通过调节 miR-490-3p/MAPK1 轴减少了异种移植肿瘤的生长。
体内外敲低 LINC00483 通过增加 miR-490-3p 和减少 MAPK1 抑制了胃癌的发展，阐明了一种理解胃癌发展的新机制。
