LINC01287/miR-298/STAT3 反馈环路调控肝癌细胞的生长和上皮间质转化表型。
LINC01287/miR-298/STAT3 feedback loop regulates growth and the epithelial-to-mesenchymal transition phenotype in hepatocellular carcinoma cells.
机构信息
Department of Hepatobiliary Surgery, Gaozhou People's Hospital, Gaozhou, China.
Department of General Surgery, The First Affiliated Hospital of BaoTou Medical University, Baotou, Inner Mongolia, China.
出版信息
J Exp Clin Cancer Res. 2018 Jul 13;37(1):149. doi: 10.1186/s13046-018-0831-2.
BACKGROUND
The long non-coding RNAs (lncRNAs) have participated in the promotion of hepatocellular carcinoma (HCC) initiation and progression. Nevertheless, the biological role and underlying mechanism of LINC01287 in HCC has never been reported.
METHODS
The TGCA database was used to explore the abnormal expression of lncRNAs in HCC. Real-time PCR and in situ hybridization assays were used to examine the expression of LINC01287 in HCC tissues. The clinicopathological characteristics of HCC patients in relation to LINC01287 expression were then analyzed. Infection of cells with the si-LINC01287 lentiviral vector was performed to down-regulate LINC01287 expression in HCC cells. MTT and colony formation assays were performed to examine cell growth ability, and FACS analysis was performed to examine the cell cycle and apoptosis. A Boyden assay was used to examine HCC cell invasion ability, and RNA immunoprecipitation tested the interaction between LINC01287 and miR-298. A luciferase reporter assay was used to examine whether STAT3 was a direct target of miR-298, and chromatin immunoprecipitation (ChIP) was used to examine the potential binding of c-jun to the miR-298 promoter.
RESULTS
We revealed that the expression of LINC01287 was increased in HCC cell lines, as well as tissues. Knockdown of LINC01287 decreased HCC cell growth and invasion both in vitro and in vivo. LINC01287 can negatively regulate miR-298 expression by acting as a ceRNA. miR-298 directly targeted STAT3 and inhibited its expression. LINC01287 exerted its function via the miR-298/STAT3 axis in HCC. Interestingly, STAT3 elevated LINC01287 expression via c-jun, which bound to the LINC01287 promoter. A feedback loop was also discovered between LINC01287 and the miR-298/STAT3 axis.
CONCLUSIONS
Our data indicated that LINC01287 played an oncogenic role in HCC growth and metastasis and that this lncRNA might serve as a novel molecular target for the treatment of HCC.
背景
长链非编码 RNA（lncRNAs）参与了肝细胞癌（HCC）的发生和发展。然而，LINC01287 在 HCC 中的生物学作用和潜在机制尚未被报道。
方法
使用 TCGA 数据库来探索 HCC 中 lncRNAs 的异常表达。实时 PCR 和原位杂交检测 HCC 组织中 LINC01287 的表达。然后分析 HCC 患者的临床病理特征与 LINC01287 表达的关系。通过慢病毒载体感染细胞来下调 HCC 细胞中的 LINC01287 表达。MTT 和集落形成实验检测细胞生长能力，FACS 分析检测细胞周期和凋亡。Boyden 实验检测 HCC 细胞侵袭能力，RNA 免疫沉淀检测 LINC01287 与 miR-298 的相互作用。荧光素酶报告基因实验检测 STAT3 是否是 miR-298 的直接靶标，染色质免疫沉淀（ChIP）检测 c-jun 与 miR-298 启动子的潜在结合。
结果
我们发现 LINC01287 在 HCC 细胞系和组织中的表达增加。LINC01287 的敲低减少了 HCC 细胞在体外和体内的生长和侵袭。LINC01287 可以通过充当 ceRNA 来负调控 miR-298 的表达。miR-298 直接靶向 STAT3 并抑制其表达。LINC01287 通过 HCC 中的 miR-298/STAT3 轴发挥其功能。有趣的是，STAT3 通过结合到 LINC01287 启动子上的 c-jun 来上调 LINC01287 的表达。还发现了 LINC01287 和 miR-298/STAT3 轴之间的反馈回路。
结论
我们的数据表明，LINC01287 在 HCC 的生长和转移中发挥致癌作用，并且这种 lncRNA 可能成为 HCC 治疗的新的分子靶标。
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