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The circSNX14 functions as a tumor suppressor via the miR-562/ LATS2 pathway in hepatocellular carcinoma cells
Journal of Molecular Histology ( IF 3.2 ) Pub Date : 2023-10-20 , DOI: 10.1007/s10735-023-10157-2
Yan Wu 1 , Yaowei Yang 1 , Xin Yi 1 , Liwen Song 1
Affiliation  

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.



中文翻译:

circSNX14 在肝细胞癌细胞中通过 miR-562/LATS2 通路发挥肿瘤抑制因子的作用

环状RNA(circRNA)在各种癌症的发生和进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然很大程度上未知。通过 qRT-PCR 分析 HCC 组织和细胞系中的 CircSNX14 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查了 circSNX14 在 HCC 细胞肿瘤发生中的作用。circSNX14、miR-562 和大肿瘤抑制激酶 2 (LATS2) mRNA 之间的相互作用通过荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 分析得到证实。CircSNX14在HCC组织和细胞系中显着下调,其下调与HCC患者的不良预后相关。在随后的功能实验中,circSNX14过表达显着抑制HCC细胞的增殖和侵袭,并减弱间充质状态。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和miR-562的相互作用,并且miR-562可以通过与LATS2的mRNA相互作用来抑制LATS2的表达。HCC 样本中的 Pearson 相关性已证实 circSNX14 与 miR-562 负相关、miR-562 与 LATS2 负相关以及 circSNX14 与 LATS2 正相关。总的来说,这些结果揭示了 circSNX14/miR-562/LATS2 轴在调节 HCC 癌症进展的恶性进展中的新作用,表明 circSNX14 的肿瘤抑制作用及其作为预后生物标志物的潜力。

更新日期:2023-10-20
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