Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancies. However, the underlying cellular mechanisms of circRNAs implicated in the pathogenesis of HCC remain unknown. In this study, we identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and we further identified that circMRPS35 was highly expressed in 35 pairs of HCC from patients. Moreover, knockdown of the expression of circMRPS35 in Huh-7 and HCC-LM3 cells suppressed their proliferation, migration, invasion, clone formation, and cell cycle in vitro, and it suppressed tumor growth in vivo as well. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), regulating the expression of Syntaxin 3 (STX3), which modulated the ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Unexpectedly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC. These results demonstrated that circMRPS35 might be a novel mediator in HCC progress, and they raise the potential of a new biomarker for HCC diagnosis and prognosis, as well as a novel therapeutic target for HCC patients.

肝细胞癌 (HCC) 是全世界癌症相关死亡的主要原因之一。据报道，环状 RNA (circRNA) 是一类新型的非编码 RNA，与多种恶性肿瘤的病因有关。然而，与 HCC 发病机制有关的 circRNA 的潜在细胞机制仍然未知。在这项研究中，我们使用一组计算分析从公共肿瘤数据库中鉴定了一种功能性 RNA hsa_circ_0000384 (circMRPS35)，并且我们进一步鉴定了 circMRPS35 在来自患者的 35 对 HCC 中高表达。此外，敲低 Huh-7 和 HCC-LM3 细胞中 circMRPS35 的表达可抑制其体外增殖、迁移、侵袭、克隆形成和细胞周期，并抑制体内肿瘤生长以及。从机械上讲，circMRPS35 吸收 microRNA-148a-3p (miR-148a)，调节突触融合蛋白 3 ( STX3 ) 的表达，后者调节磷酸酶和张力蛋白同系物 (PTEN) 的泛素化和降解。出乎意料的是，我们检测到一种由 circMRPS35 (circMRPS35-168aa) 编码的肽，它被化疗药物显着诱导并促进 HCC 的顺铂耐药。这些结果表明，circMRPS35 可能是 HCC 进展中的一种新型介质，它们提高了作为 HCC 诊断和预后新生物标志物以及 HCC 患者新治疗靶点的潜力。