Department of General Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315100, Zhejiang, China.
Department of Emergency, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315100, Zhejiang, China.
Sci Rep. 2024 Apr 8;14(1):8243. doi: 10.1038/s41598-024-58708-1.
The role of circular RNA (circRNAs) in hepatocellular carcinoma (HCC) has been extensively studied. Previous research has highlighted the regulatory role of circSNX6 in HCC cells and tissues. However, the precise mechanism underlying HCC progression still requires comprehensive investigation. The study initially utilized quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess circSNX6 expression levels in HCC cell lines and tissues. Subsequently, the stability of circRNA was evaluated through Ribonuclease R and actinomycin D treatment assays. The impact of circSNX6 knockdown on proliferation, migration, invasion, and angiogenesis abilities was determined using various assays including colony formation, Transwell culture system, tube formation assay, and cell counting kit (CCK)-8 assays. Additionally, RNA immunoprecipitation chip and dual-luciferase reporter assays were employed to investigate the interactions between circSNX6 and miR-383-5p. Finally, an HCC xenograft tumor model in mice was established to assess the in vivo expression of circSNX6 and its functional role in HCC. Our findings revealed an elevated circSNX6 expression in HCC tissues, which was correlated with poor patient prognosis. Knockdown of circSNX6 suppressed HCC cell growth, invasion, metastasis, and angiogenesis. The downregulation of miR-383-5p, a target of circSNX6, significantly attenuated the tumor-suppressive effects induced by circSNX6 knockdown. Moreover, circSNX6 was found to modulate VEGFA expression by targeting miR-383-5p. The inhibition of HCC cell proliferation by miR-383-5p could be partially reversed by overexpressing VEGFA. Silencing circSNX6 also suppressed tumor formation and the metastasis of HCC cells in a mouse model. In summary, our findings suggest that circSNX6 promotes cell proliferation, metastasis, and angiogenesis in HCC by regulating the miR-383-5p/VEGFA pathway.
环状 RNA (circRNAs) 在肝细胞癌 (HCC) 中的作用已经得到了广泛的研究。先前的研究强调了 circSNX6 在 HCC 细胞和组织中的调控作用。然而，HCC 进展的确切机制仍需要全面研究。该研究首先利用定量逆转录聚合酶链反应 (qRT-PCR) 评估 HCC 细胞系和组织中 circSNX6 的表达水平。随后，通过核糖核酸酶 R 和放线菌素 D 处理实验评估 circRNA 的稳定性。使用各种实验，包括集落形成实验、Transwell 培养系统、管形成实验和细胞计数试剂盒 (CCK)-8 实验，评估 circSNX6 敲低对增殖、迁移、侵袭和血管生成能力的影响。此外，采用 RNA 免疫沉淀芯片和双荧光素酶报告基因实验研究 circSNX6 与 miR-383-5p 之间的相互作用。最后，建立 HCC 异种移植肿瘤模型在小鼠体内评估 circSNX6 的表达及其在 HCC 中的功能作用。我们的研究结果表明，HCC 组织中 circSNX6 的表达升高，与患者预后不良相关。circSNX6 的敲低抑制 HCC 细胞生长、侵袭、转移和血管生成。circSNX6 的下调显著减弱了 circSNX6 敲低诱导的肿瘤抑制作用。此外，circSNX6 通过靶向 miR-383-5p 调节 VEGFA 的表达。miR-383-5p 抑制 HCC 细胞增殖的作用可以通过过表达 VEGFA 部分逆转。沉默 circSNX6 也抑制了小鼠模型中 HCC 细胞的肿瘤形成和转移。综上所述，我们的研究结果表明，circSNX6 通过调节 miR-383-5p/VEGFA 通路促进 HCC 细胞的增殖、转移和血管生成。
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