Central Laboratory, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266071, China.
Int Immunopharmacol. 2024 Jul 30;136:112297. doi: 10.1016/j.intimp.2024.112297. Epub 2024 May 29.
RNA-binding proteins are revealed to play important roles during the progression of hepatocellular carcinoma (HCC). However, the regulatory mechanisms of RNA-binding protein Quaking (QKI) in the expression and role of long non-coding RNAs (lncRNAs) in HCC cells remain not well understood.
Cell Counting Kit-8, wound-healing, Transwell and colony-forming assays were performed to evaluate the effects of QKI and lncRNA EGOT on proliferation and migration of HCC cells. Tumor growth of HCC was analyzed using a mouse xenograft model. Immunoprecipitation (RIP) assay was used to investigate the interaction between QKI and EGOT.
The expression of QKI was significantly upregulated in HCC tissues and the higher QKI level was significantly associated with a poorer prognosis. Overexpression of QKI promoted the proliferation, migration, and colony-forming ability of HCC cells in vitro and tumor growth of HCC in vivo. Mechanistically, QKI protein could bind to EGOT RNA and increase its expression. Inhibition of EGOT attenuated the effects of QKI on the malignant phenotypes of HCC cells. In addition, both QKI and EGOT could activate the SAPK/JNK signaling pathway in HCC cells.
Our findings indicated that QKI exerted promotive effects on the malignant phenotypes of HCC through its interaction with EGOT.
RNA 结合蛋白在肝细胞癌 (HCC) 的进展中被发现起着重要作用。然而，RNA 结合蛋白 Quaking (QKI) 在 HCC 细胞中长链非编码 RNA (lncRNA) 的表达和作用的调控机制仍不清楚。
使用细胞计数试剂盒-8、划痕愈合、Transwell 和集落形成实验来评估 QKI 和 lncRNA EGOT 对 HCC 细胞增殖和迁移的影响。使用小鼠异种移植模型分析 HCC 肿瘤的生长。免疫沉淀 (RIP) 实验用于研究 QKI 和 EGOT 之间的相互作用。
QKI 在 HCC 组织中的表达显著上调，较高的 QKI 水平与预后较差显著相关。QKI 的过表达促进 HCC 细胞在体外的增殖、迁移和集落形成能力以及体内 HCC 的肿瘤生长。机制上，QKI 蛋白可以与 EGOT RNA 结合并增加其表达。EGOT 的抑制减弱了 QKI 对 HCC 细胞恶性表型的影响。此外，QKI 和 EGOT 均可激活 HCC 细胞中的 SAPK/JNK 信号通路。
我们的研究结果表明，QKI 通过与 EGOT 的相互作用对 HCC 的恶性表型发挥促进作用。
