Xu Lin, Liu Daiting, Wang Xun
Digestion Medicine Department, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430063, China.
Korean J Physiol Pharmacol. 2023 May 1;27(3):197-208. doi: 10.4196/kjpp.2023.27.3.197.
Dysregulation of certain long non-coding RNAs may facilitate tumor initiation and progression. However, numerous carcinogenesis-related long non-coding RNAs have not been characterized. The goal of this study was to elucidate the role of LINC00562 in gastric cancer (GC). The expression of LINC00562 was analyzed using real-time quantitative PCR and Western blotting. The proliferative capacity of GC cells was determined using Cell Counting Kit-8 and colony-formation assays. The migration of GC cells were evaluated using wound-healing assays. The apoptosis of GC cells was assessed by measuring the expression levels of apoptosis-related proteins (Bax and Bcl-2). Xenograft models in nude mice were constructed for functional analysis of LINC00562. The binding relationship between miR-4636 and LINC00562 or adaptor protein complex 1 sigma 3 (AP1S3), obtained from public databases, was confirmed using dual-luciferase and RNA-binding protein immunoprecipitation experiments. LINC00562 was expressed in GC cells at high levels. Knockdown of LINC00562 repressed GC cell growth and migration, promoted apoptosis , and inhibited tumor growth in nude mouse models. LINC00562 directly targeted miR-4636, and miR-4636 depletion restored the GC cell behavior inhibited by LINC00562 absence. AP1S3, an oncogene, binds to miR-4636. MiR-4636 downregulation increased AP1S3 level, restoring GC cell malignant behaviors inhibited by AP1S3 downregulation. Thus, LINC00562 exerts carcinogenic effects on GC development by targeting miR-4636-mediated AP1S3 signaling.
某些长链非编码RNA的失调可能促进肿瘤的发生和发展。然而，许多与致癌作用相关的长链非编码RNA尚未得到表征。本研究的目的是阐明LINC00562在胃癌（GC）中的作用。使用实时定量PCR和蛋白质印迹法分析LINC00562的表达。使用细胞计数试剂盒-8和集落形成试验测定GC细胞的增殖能力。使用伤口愈合试验评估GC细胞的迁移。通过测量凋亡相关蛋白（Bax和Bcl-2）的表达水平来评估GC细胞的凋亡。构建裸鼠异种移植模型以对LINC00562进行功能分析。使用双荧光素酶和RNA结合蛋白免疫沉淀实验，证实了从公共数据库获得的miR-4636与LINC00562或衔接蛋白复合物1西格玛3（AP1S3）之间的结合关系。LINC00562在GC细胞中高水平表达。敲低LINC00562可抑制GC细胞生长和迁移，促进凋亡，并抑制裸鼠模型中的肿瘤生长。LINC00562直接靶向miR-4636，miR-4636的缺失恢复了因LINC00562缺失而受到抑制的GC细胞行为。AP1S3是一种癌基因，可与miR-4636结合。miR-4636的下调增加了AP1S3水平，恢复了因AP1S3下调而受到抑制的GC细胞恶性行为。因此，LINC00562通过靶向miR-4636介导的AP1S3信号传导对GC的发展发挥致癌作用。
