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Hsa_circ_0079875 作为竞争性内源性 RNA 促进肝癌进展。

Hsa_circ_0079875 functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression.

机构信息

Nantong University Medical School, Nantong, Jiangsu, China.

Department of Clinical Laboratory, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, Jiangsu, China.

出版信息

Cell Cycle. 2024 Mar;23(5):519-536. doi: 10.1080/15384101.2024.2345469. Epub 2024 Apr 29.

Abstract

Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 . Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis . Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.

摘要

环状 RNA(circRNA)可以作为竞争性内源性 RNA(ceRNA)影响肝细胞癌(HCC)的发展。然而,仍有许多 circRNA 的功能未知。我们的研究探讨了一种新型 circRNA,hsa_circ_0079875,在 HCC 中的作用。通过下一代测序、定量逆转录聚合酶链反应(qRT-PCR)和荧光原位杂交(FISH)验证了 hsa_circ_0079875 在 HCC 中的表达。通过 RNA 亚细胞分离和 FISH 实验研究了 hsa_circ_0079875 在 HCC 细胞中的分布。通过过表达和敲低 hsa_circ_0079875 验证了对 HCC 增殖、侵袭、迁移、细胞周期和凋亡的功能影响。此外,还使用异种移植小鼠模型和免疫组织化学实验评估了 hsa_circ_0079875 的功能。hsa_circ_0079875 在 HCC 组织中上调,主要分布在细胞质中。较高的 hsa_circ_0079875 导致更大的肿瘤组织、更多的微血管侵犯(MVI)和更高的 AFP 水平,进而导致预后不良。过表达 hsa_circ_0079875 可以促进 HCC 细胞的增殖、迁移和侵袭,抑制凋亡。敲低 hsa_circ_0079875 则有相反的效果。测序和生物信息预测了 hsa_circ_0079875 的靶 miRNA 和 mRNA。进一步的生物信息学和临床相关性分析表明,hsa_circ_0079875 通过 hsa_circ_0079875/miR-519d-59/NRAS ceRNA 网络促进 HCC 的恶性生物学行为。因此,hsa_circ_0079875 可以作为 HCC 的潜在预后标志物和治疗靶点。

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