Medical School of Nantong University, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, Jiangsu, China.
Nantong Haimen People's Hospital, Nantong, Jiangsu, China.
Int Immunopharmacol. 2024 Oct 25;140:112873. doi: 10.1016/j.intimp.2024.112873. Epub 2024 Aug 3.
Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with poor prognosis. Using high-throughput sequencing, we identified a novel circRNA, circGNAO1, which is downregulated in HCC tissues compared to adjacent tissues. However, the potential functions and mechanisms of circGNAO1 in HCC metastasis remain unclear.
qRT-PCR was used to detect the expression of circGNAO1, miR-182-5p, and FOXO1 in HCC cells and tissues. Bioinformatics analysis, RNA pull-down assyas, and dual-luciferase reporter assays were employed to verify the interaction between circGNAO1 and miR-182-5p. Functional experiments were conducted using circGNAO1 overexpression and knockdown cell lines, including Transwell, wound healing, and EdU assays. Liver metastasis models and subcutaneous xenograft mouse models were established to analyze the effect of circGNAO1 on HCC metastasis and growth in vivo.
High-throughput sequencing and qRT-PCR results showed that the expression of circGNAO1 dramatically decreased in HCC tissues. Functionally, in vivo and in vitro experiments verified that overexpression of circGNAO1 inhibited the proliferation, migration, invasion and EMT of HCC cells, while knockdown of circGNAO1 promoted these behaviors. Mechanistically, we have demonstrated that circGNAO1 functions as a sponge for miR-182-5p to regulate FOXO1 expression, thereby activating the TGF-β/Smad3 signaling pathway and EMT process.
circGNAO1 suppresses the progression and metastasis of HCC through the miR-182-5p/FOXO1 axis, and circGNAO1 may be an efficient therapeutic target in HCC.
肝细胞癌（HCC）是一种预后不良的侵袭性恶性肿瘤。通过高通量测序，我们鉴定出一种新型环状 RNA，circGNAO1，其在 HCC 组织中的表达低于相邻组织。然而，circGNAO1 在 HCC 转移中的潜在功能和机制尚不清楚。
qRT-PCR 用于检测 HCC 细胞和组织中 circGNAO1、miR-182-5p 和 FOXO1 的表达。生物信息学分析、RNA 下拉测定和双荧光素酶报告基因测定用于验证 circGNAO1 与 miR-182-5p 的相互作用。使用 circGNAO1 过表达和敲低细胞系进行功能实验，包括 Transwell、划痕愈合和 EdU 测定。建立肝转移模型和皮下异种移植小鼠模型，分析 circGNAO1 对 HCC 转移和体内生长的影响。
高通量测序和 qRT-PCR 结果表明 circGNAO1 在 HCC 组织中的表达显著降低。功能上，体内和体外实验验证了过表达 circGNAO1 抑制 HCC 细胞的增殖、迁移、侵袭和 EMT，而敲低 circGNAO1 则促进了这些行为。机制上，我们已经证明 circGNAO1 作为 miR-182-5p 的海绵，调节 FOXO1 表达，从而激活 TGF-β/Smad3 信号通路和 EMT 过程。
circGNAO1 通过 miR-182-5p/FOXO1 轴抑制 HCC 的进展和转移，circGNAO1 可能是 HCC 有效的治疗靶点。
