Department of General Surgery, the Sanya Hongsen Hospital of Harbin Medical University, Fenghuang Road, Sanya, 572000, China.
Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
J Exp Clin Cancer Res. 2018 Sep 10;37(1):222. doi: 10.1186/s13046-018-0896-y.
Emerging evidence has shown long noncoding RNAs (lncRNAs) exert important roles in colorectal cancer (CRC) tumorigenesis. However, most lncRNAs involved in this process remain undefined and the underlying molecular mechanisms mediated by lncRNAs are largely unknown.
An unbiased screening was used to identify novel lncRNAs involved in CRC according to an online-available data dataset. In situ hybridization (ISH) and qRT-PCR was used to detect lncRNA expression patterns. CCK8, colony formation, fluorescence activated cell sorter (FACS), transwell, xenograft nude mouse model and western blot assays were used to analyze the functions of SLCO4A1-AS1. RNA-pulldown, western blot, RNA fluorescence in situ hybridization (RNA-FISH) and electrophoretic mobility shift assay (EMSA) assays were utilized to explore the molecular mechanism of SLCO4A1-AS1.
LncRNA SLCO4A1-AS1 was significantly upregulated in CRC tissues and its overexpression was closely related with poor prognosis and tumor metastasis. By knocking down SLCO4A1-AS1, we found that SLCO4A1-AS1 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of CRC cells in vitro, as well as inhibited cell apoptosis. Moreover, SLCO4A1-AS1 dramatically delayed tumor propagation in vivo. Mechanistically, SLCO4A1-AS1 activates Wnt/β-catenin signaling. SLCO4A1-AS1 enhanced the stability of β-catenin by impairing the interaction of β-catenin with GSKβ and inhibiting its phosphorylation. Finally, restoration of β-catenin protein level rescued the proliferation, migration and invasion in SLCO4A1-AS1-depleted CRC cells.
SLCO4A1-AS1 serves as an oncogenic role in CRC through activating Wnt/β-catenin signaling pathway. And SLCO4A1-AS1 might be a useful biomarker for CRC diagnosis and prognosis.
新兴证据表明，长非编码 RNA（lncRNA）在结直肠癌（CRC）肿瘤发生中发挥重要作用。然而，在此过程中涉及的大多数 lncRNA 尚未确定，lncRNA 介导的潜在分子机制在很大程度上尚不清楚。
根据在线可用数据集，使用无偏筛选来鉴定参与 CRC 的新型 lncRNA。原位杂交（ISH）和 qRT-PCR 用于检测 lncRNA 表达模式。CCK8、集落形成、荧光激活细胞分选（FACS）、transwell、异种移植裸鼠模型和 Western blot 测定用于分析 SLCO4A1-AS1 的功能。RNA 下拉、Western blot、RNA 荧光原位杂交（RNA-FISH）和电泳迁移率变动分析（EMSA）测定用于探索 SLCO4A1-AS1 的分子机制。
lncRNA SLCO4A1-AS1 在 CRC 组织中显著上调，其过表达与不良预后和肿瘤转移密切相关。通过敲低 SLCO4A1-AS1，我们发现 SLCO4A1-AS1 促进了 CRC 细胞在体外的增殖、迁移、侵袭和上皮-间充质转化（EMT），并抑制了细胞凋亡。此外，SLCO4A1-AS1 显著延缓了体内肿瘤的增殖。机制上，SLCO4A1-AS1 通过损害β-catenin 与 GSKβ 的相互作用并抑制其磷酸化来激活 Wnt/β-catenin 信号通路。最后，β-catenin 蛋白水平的恢复挽救了 SLCO4A1-AS1 耗尽的 CRC 细胞中的增殖、迁移和侵袭。
SLCO4A1-AS1 通过激活 Wnt/β-catenin 信号通路在 CRC 中发挥致癌作用。并且 SLCO4A1-AS1 可能是 CRC 诊断和预后的有用生物标志物。
