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环状RNA hsa_circ_0001394通过靶向miR-527/UBE2A轴促进肝细胞癌进展。

The circular RNA hsa_circ_0001394 promotes hepatocellular carcinoma progression by targeting the miR-527/UBE2A axis.

作者信息

Yan Yu, Nie Yu, Peng Chun, Xing Fuchen, Ji Saiguang, Liu Hong, Zhu Chuandong

机构信息

Department of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China.

Department of Thoracic Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China.

出版信息

Cell Death Discov. 2022 Feb 24;8(1):81. doi: 10.1038/s41420-022-00866-0.

Abstract

Circular RNAs (circRNAs) have been recognized as significant participants in the progression of different cancers; however, the detailed mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain unclear. In this study, hsa_circ_0001394 was identified by RNA-seq analysis, and hsa_circ_0001394 was determined to be highly expressed in HCC specimens and cell lines. Patients with high expression of hsa_circ_0001394 tended to exhibit poor survival. Increased hsa_circ_0001394 expression in plasma was closely correlated with clinicopathological features including elevated vascular invasion and an advanced TNM stage, as indicated by alpha-fetoprotein (AFP) analysis. Hsa_circ_0001394 promoted the proliferation, migration, and invasion of HCC cells, whereas knockdown of hsa_circ_0001394 inhibited HCC tumorigenesis in vivo. In addition, mechanistic studies showed that miR-527 negatively interacted with hsa_circ_0001394. Furthermore, UBE2A was revealed to serve as a target of miR-527. Overall, the present study suggested that hsa_circ_0001394 may function as a sponge to promote HCC progression by regulating the miR-527/UBE2A pathway. Thus, hsa_circ_0001394 may become a promising biomarker and potential therapeutic target in HCC treatment.

摘要

环状RNA(circRNAs)已被公认为是不同癌症进展中的重要参与者;然而,circRNAs在肝细胞癌(HCC)中的详细机制仍不清楚。在本研究中,通过RNA测序分析鉴定出hsa_circ_0001394,并且确定hsa_circ_0001394在HCC标本和细胞系中高表达。hsa_circ_0001394高表达的患者往往生存较差。如甲胎蛋白(AFP)分析所示,血浆中hsa_circ_0001394表达增加与包括血管侵犯增加和TNM分期晚期在内的临床病理特征密切相关。Hsa_circ_0001394促进HCC细胞的增殖、迁移和侵袭,而敲低hsa_circ_0001394在体内抑制HCC肿瘤发生。此外,机制研究表明miR-527与hsa_circ_0001394负向相互作用。此外,UBE2A被揭示为miR-527的靶标。总体而言,本研究表明hsa_circ_0001394可能作为海绵,通过调节miR-527/UBE2A途径促进HCC进展。因此,hsa_circ_0001394可能成为HCC治疗中有前景的生物标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bfd/8873434/d35eb0e71459/41420_2022_866_Fig1_HTML.jpg

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