SATB1 3'-UTR 和 lncRNA-UCA1 竞争性结合 miR-495-3p，并共同调节胃癌的增殖和侵袭。
SATB1 3'-UTR and lncRNA-UCA1 competitively bind to miR-495-3p and together regulate the proliferation and invasion of gastric cancer.
机构信息
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
First Clinical Medical College of Hubei University of Chinese Medcine, Wuhan, China.
出版信息
J Cell Biochem. 2019 Apr;120(4):6671-6682. doi: 10.1002/jcb.27963. Epub 2018 Oct 28.
High expression of special AT-rich-binding protein 1 (SATB1) correlates with the advanced TNM stage and short overall and recurrence-free survival of gastric cancer (GC). A bioinformatic analysis revealed that SATB1 3'-untranslated region (3'-UTR) and long noncoding RNA UCA1 (lncRNA-UCA1) might competitively bind to microRNA-495-3p (miR-495-3p). Interestingly, lncRNA-UCA1 is also an important contributor to GC. The current study aimed to demonstrate the potential interaction among SATB1/miR-495-3p/lncRNA-UCA1 network and their effects on GC proliferation and invasion. The expression in GC and paracancerous normal tissues were assessed using real-time polymerase chain reaction and Western blot analysis. Luciferase reporter, RNA pull-down, and transfection assays were performed to determine the interaction among SATB1/miR-495-3p/lncRNA-UCA1 network in GC cells. GC proliferation and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, and colony formation assays. Results showed higher expression of SATB1 and lncRNA-UCA1 but lower miR-495-3p expression in GC than in the normal tissues. In luciferase reporter assay, miR-495-3p bound to three seed sequences in SATB1 3'-UTR but only one in lncRNA-UCA1. SATB1 knockdown increased the combination of miR-495-3p with lncRNA-UCA1 but decreased lncRNA-UCA1 expression. Decreased lncRNA-UCA1 was also observed with the mimics increased miR-495-3p. These data suggested that SATB1 3'-UTR functions as a competing endogenous RNA of miR-495-3p and positively regulates lncRNA-UCA1. LncRNA-UCA1 knockdown only decreased SATB1 expression in MKN-45 cells but not in BGC-823 cells, which suggested that the regulatory effect of lncRNA-UCA1 on SATB1 by sponging miR-495-3p is cell-dependent. This study further identified that SATB1/miR-495-3p/lncRNA-UCA1 network is implicated in GC proliferation and invasion. The current study firstly revealed that SATB1 interacts with miR-495-3p/lncRNA-UCA1 network, whereby enhancing GC proliferation and invasion.
SATB1 高表达与胃癌（GC）的晚期 TNM 分期和总生存及无复发生存时间缩短相关。生物信息学分析显示，SATB1 3'非翻译区（3'-UTR）和长链非编码 RNA UCA1（lncRNA-UCA1）可能与 microRNA-495-3p（miR-495-3p）竞争性结合。有趣的是，lncRNA-UCA1 也是 GC 的一个重要贡献者。本研究旨在证实 SATB1/miR-495-3p/lncRNA-UCA1 网络之间的潜在相互作用及其对 GC 增殖和侵袭的影响。采用实时聚合酶链反应和 Western blot 分析评估 GC 和癌旁正常组织中的表达。通过荧光素酶报告、RNA 下拉和转染实验确定 GC 细胞中 SATB1/miR-495-3p/lncRNA-UCA1 网络的相互作用。通过 3-(4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐、Transwell 侵袭和集落形成实验评估 GC 增殖和侵袭。结果显示，GC 组织中 SATB1 和 lncRNA-UCA1 的表达高于正常组织，而 miR-495-3p 的表达则较低。在荧光素酶报告实验中，miR-495-3p 与 SATB1 3'-UTR 的三个种子序列结合，但与 lncRNA-UCA1 仅结合一个。SATB1 敲低增加了 miR-495-3p 与 lncRNA-UCA1 的结合，但降低了 lncRNA-UCA1 的表达。miR-495-3p 模拟物增加也观察到 lncRNA-UCA1 减少。这些数据表明，SATB1 3'-UTR 作为 miR-495-3p 的竞争内源性 RNA，正向调节 lncRNA-UCA1。lncRNA-UCA1 敲低仅降低 MKN-45 细胞中的 SATB1 表达，而不降低 BGC-823 细胞中的 SATB1 表达，这表明 lncRNA-UCA1 通过海绵 miR-495-3p 对 SATB1 的调节作用是细胞依赖性的。本研究进一步证实，SATB1/miR-495-3p/lncRNA-UCA1 网络参与 GC 的增殖和侵袭。本研究首次揭示 SATB1 与 miR-495-3p/lncRNA-UCA1 网络相互作用，从而增强 GC 的增殖和侵袭。
Zotero 插件