新的证据表明环状 RNA (circRNA) 在癌症发生和进展中发挥着关键作用。了解 circRNA 在肿瘤发展中的功能和潜在机制有望发现新的诊断指标和治疗靶点。在本研究中，我们的重点是阐明hsa-circ-0003764在肝细胞癌（HCC）中的功能和调控机制。从circbase数据库中鉴定出新发现的hsa-circ-0003764（circPTPN12）。利用 QRT-PCR 分析评估 HCC 组织和细胞中 hsa-circ-0003764 的表达水平。我们进行了体外和体内实验来检查 circPTPN12 对 HCC 细胞增殖和凋亡的影响。此外，还采用 RNA 测序、RNA 免疫沉淀、生物素偶联探针 Pull-down 测定和 FISH 来确认和建立 hsa-circ-0003764、PDLIM2、OTUD6B、P65 和 ESRP1 之间的关系。在 HCC 中， circPTPN12 与不良预后相关。 CircPTPN12 在体外和体内均表现出对 HCC 细胞增殖的抑制作用。从机制上讲，RNA 测序分析揭示了 NF-κB 信号通路是 circPTPN12 的靶向通路。在功能上，circPTPN12被发现与PDLIM2的PDZ结构域相互作用，促进P65的泛素化。此外，circPTPN12 通过促进 PDLIM2 的去泛素化来增强 PDLIM2/OTUD6B 复合物的组装。 ESRP1 被确定与 pre-PTPN12 结合，从而促进 circPTPN12 的产生。总的来说，我们的研究结果表明 circPTPN12 参与调节 PDLIM2 功能，影响 HCC 进展。已确定的 ESRP1/circPTPN12/PDLIM2/NF-κB 轴有望成为 HCC 背景下的新型治疗靶点。© 2024。作者。

Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular carcinoma (HCC).A newly discovered hsa-circ-0003764 (circPTPN12) was identified from the circbase database. QRT-PCR analysis was utilized to assess the expression levels of hsa-circ-0003764 in both HCC tissues and cells. We conducted in vitro and in vivo experiments to examine the impact of circPTPN12 on the proliferation and apoptosis of HCC cells. Additionally, RNA-sequencing, RNA immunoprecipitation, biotin-coupled probe pull-down assays, and FISH were employed to confirm and establish the relationship between hsa-circ-0003764, PDLIM2, OTUD6B, P65, and ESRP1.In HCC, the downregulation of circPTPN12 was associated with an unfavorable prognosis. CircPTPN12 exhibited suppressive effects on the proliferation of HCC cells both in vitro and in vivo. Mechanistically, RNA sequencing assays unveiled the NF-κB signaling pathway as a targeted pathway of circPTPN12. Functionally, circPTPN12 was found to interact with the PDZ domain of PDLIM2, facilitating the ubiquitination of P65. Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2. ESRP1 was identified to bind to pre-PTPN12, thereby fostering the generation of circPTPN12.Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC.© 2024. The Author(s).