You Liting, Wu Qian, Xin Zhaodan, Zhong Huiyu, Zhou Juan, Jiao Lin, Song Xingbo, Ying Binwu
Department of Laboratory Medicine, West China Hospital, Sichuan University, 37, Guoxue Lane, Chengdu, 610041, Sichuan, China.
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Cancer Cell Int. 2021 Oct 29;21(1):576. doi: 10.1186/s12935-021-02255-6.
miR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge.
Luciferase reporter assay was conducted to verify the binding of miR-124-3p and HOXA11-AS. RT-PCR and western blot were performed to detect the expression of HOXA11-AS, miR-124-3p and ITGB3 in GC tissues and cells. Gene silence and overexpression experiments as well as cell migration and invasion assays on GC cell lines were performed to determine the regulation of molecular pathways, HOXA11-AS/miR-124-3p/ITGB3. Furthermore, the role of HOXA11-AS in GC was confirmed in mice models.
We found HOXA11-AS is up-regulated in GC tissues and can bind with miR-124-3p. Through overexpression/knockdown experiments and function tests in vitro, we demonstrated HOXA11-AS can promote ITGB3 expression by sponging miR-124-3p, consequently enhance the proliferation, migration, and invasion of GC cells. Meanwhile, we validated that HOXA11-AS promotes migration and invasion of GC cells via down-regulating miR-124-3p and up-regulating ITGB3 in vivo.
We demonstrated that lncRNA HOXA11-AS can increase ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Our results suggested that HOXA11-AS may reasonably serve as a promising diagnostic biomarker and a potential therapeutic target of GC.
miR-124-3p可抑制整合素β3（ITGB3）表达，从而抑制胃癌（GC）的迁移和侵袭，在此过程中，长链非编码RNA HOXA11-AS可能充当分子海绵。
进行荧光素酶报告基因检测以验证miR-124-3p与HOXA11-AS的结合。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测GC组织和细胞中HOXA11-AS、miR-124-3p和ITGB3的表达。对GC细胞系进行基因沉默和过表达实验以及细胞迁移和侵袭实验，以确定分子通路HOXA11-AS/miR-124-3p/ITGB3的调控作用。此外，在小鼠模型中证实了HOXA11-AS在GC中的作用。
我们发现HOXA11-AS在GC组织中上调，且能与miR-124-3p结合。通过体外过表达/敲低实验及功能测试，我们证明HOXA11-AS可通过吸附miR-124-3p促进ITGB3表达，从而增强GC细胞的增殖、迁移和侵袭能力。同时，我们在体内验证了HOXA11-AS通过下调miR-124-3p和上调ITGB3促进GC细胞的迁移和侵袭。
我们证明长链非编码RNA HOXA11-AS可通过吸附miR-124-3p增加ITGB3表达，从而促进胃癌的迁移和侵袭。我们的结果表明，HOXA11-AS有望成为一种有前景的诊断生物标志物和GC的潜在治疗靶点。
