Wu Yan, Yang Yaowei, Yi Xin, Song Liwen
Department of General Surgery, University-Town Hospital of Chongqing Medical University, No.55 University Town Middle Road, Shapingba District, Chongqing, 401331, China.
J Mol Histol. 2023 Dec;54(6):593-607. doi: 10.1007/s10735-023-10157-2. Epub 2023 Oct 20.
Circular RNAs (circRNAs) play critical roles in the initiation and progression of various cancers. However, the potential functional roles of circSNX14 in hepatocellular carcinoma (HCC) remain largely unknown. CircSNX14 expression pattern was analyzed in HCC tissues and cell lines via qRT-PCR. The effects of circSNX14 on cell proliferation, invasion, angiogenesis, and Epithelial-mesenchymal transition (EMT) were investigated by overexpression experiments. The role of circSNX14 in the tumorigenesis of HCC cells was examined using in vivo xenograft mouse model. The interaction between circSNX14, miR-562, and Large Tumor Suppressor Kinase 2 (LATS2) mRNA was confirmed by Luciferase reporter assay and RNA immunoprecipitation (RIP) analysis. CircSNX14 was significantly down-regulated in HCC tissues and cell lines, and its down-regulation was correlated with a poor prognosis in HCC patients. In the following functional experiments, circSNX14 overexpression remarkably suppressed the proliferation and invasion of HCC cells, and attenuated the mesenchymall status. circSNX14 overexpression also suppressed the tumorigenesis of HCC cells in the mouse model. We further revealed the interaction of circSNX14 and miR-562, and miR-562 could suppress the expression of LATS2 by interacting with its mRNA. The negative correlation of circSNX14 and miR-562, negative correlation of miR-562 and LATS2, and positive correlation of circSNX14 and LATS2 have been confirmed by Pearson correlation in the HCC samples. Collectively, these results reveal a novel role of circSNX14/miR-562/LATS2 axis in regulating the malignant progression of HCC cancer progression, indicating the tumor suppressor role of circSNX14 and its potential as a prognostic biomarker.
环状RNA（circRNAs）在多种癌症的发生和发展中发挥着关键作用。然而，circSNX14在肝细胞癌（HCC）中的潜在功能作用仍 largely未知。通过qRT-PCR分析了HCC组织和细胞系中circSNX14的表达模式。通过过表达实验研究了circSNX14对细胞增殖、侵袭、血管生成和上皮-间质转化（EMT）的影响。使用体内异种移植小鼠模型检测了circSNX14在HCC细胞肿瘤发生中的作用。通过荧光素酶报告基因检测和RNA免疫沉淀（RIP）分析证实了circSNX14、miR-562和大肿瘤抑制激酶2（LATS2）mRNA之间的相互作用。circSNX14在HCC组织和细胞系中显著下调，其下调与HCC患者的不良预后相关。在接下来的功能实验中，circSNX14过表达显著抑制了HCC细胞的增殖和侵袭，并减弱了间质状态。circSNX14过表达还抑制了小鼠模型中HCC细胞的肿瘤发生。我们进一步揭示了circSNX14与miR-562的相互作用，并且miR-562可通过与其mRNA相互作用抑制LATS2的表达。通过Pearson相关性分析在HCC样本中证实了circSNX14与miR-562的负相关性、miR-562与LATS2的负相关性以及circSNX14与LATS2的正相关性。总体而言，这些结果揭示了circSNX14/miR-562/LATS2轴在调节HCC癌症进展的恶性进程中的新作用，表明circSNX14的肿瘤抑制作用及其作为预后生物标志物的潜力。
