Abstract：
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. It has been proven that long non-coding RNAs (lncRNAs) play an essential role in regulating HCC progression. However, the involvement of LINC01094 in regulating epithelial-mesenchymal transition (EMT) in HCC remains unclear. LINC01094 expression in HCC patients was retrieved from the Cancer Genome Atlas database. Overexpressing and downregulating LINC01094 were conducted to investigate its biological functions using Hep3B, SNU-387, and HuH-7 cells. Western blotting and morphological observation were performed to study the EMT in HCC cells. Transwell assay was adopted to determine the migration and invasion of HCC cells. The underlying mechanism of competitive endogenous RNAs (ceRNAs) was investigated using bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction, and rescue experiments. Elevated LINC01094 expression was observed in HCC and associated with a poor prognosis. Knockdown of LINC01094 expression in SNU-387 and HuH-7 cells could inhibit migration, invasion, and EMT markers. Overexpression of LINC01094 indicated that LINC01094 promoted EMT via the TGF-β/SMAD signaling pathway. The bioinformatics analysis revealed that miR-122-5p was a target of LINC01094. The miRWalk database analysis showed that TGFBR2, SMAD2, and SMAD3 were downstream targets of miR-122-5p. Mechanically, LINC01094 acted as a ceRNA that facilitated HCC metastasis by sponging miR-122-5p to regulate the expression of TGFBR2, SMAD2, and SMAD3. Further, TGF-β1 could enhance the expression of LINC01094, forming a positive feedback loop. TGF-β1-induced LINC01094 expression promotes HCC cell migration and invasion by targeting the miR-122-5p/TGFBR2-SMAD2-SMAD3 axis. LINC01094 may be a potential prognostic biomarker and therapeutic target for HCC metastasis.
摘要：
肝细胞癌（HCC）是一种常见的恶性肿瘤，预后较差。已经证明，长链非编码RNA（lncRNA）在调节HCC进展中起着至关重要的作用。然而,LINC01094是否参与调节HCC的上皮-间质转化(EMT)尚不清楚.从癌症基因组图谱数据库检索HCC患者中的LINC01094表达。使用Hep3B进行过表达和下调LINC01094以研究其生物学功能，SNU-387和HuH-7细胞。进行蛋白质印迹和形态学观察以研究HCC细胞中的EMT。采用Transwell法检测HCC细胞的迁移和侵袭能力。使用生物信息学分析研究了竞争性内源RNA（ceRNA）的潜在机制，定量逆转录聚合酶链反应，和救援实验。在HCC中观察到升高的LINC01094表达并与不良预后相关。敲低LINC01094在SNU-387和HuH-7细胞中的表达可抑制细胞迁移,入侵,和EMT标记。LINC01094的过表达表明LINC01094通过TGF-β/SMAD信号通路促进EMT。生物信息学分析显示miR-122-5p是LINC01094的靶标。miRWalk数据库分析显示TGFBR2、SMAD2和SMAD3是miR-122-5p的下游靶标。机械上,LINC01094作为一种ceRNA，通过构建miR-122-5p来调节TGFBR2、SMAD2和SMAD3的表达，从而促进HCC转移。Further,TGF-β1可增强LINC01094的表达,形成正反馈环。TGF-β1诱导的LINC01094表达通过靶向miR-122-5p/TGFBR2-SMAD2-SMAD3轴促进HCC细胞迁移和侵袭。LINC01094可能是HCC转移的潜在预后生物标志物和治疗靶点。
