CircRNA hsa_circ_0004781 promoted cell proliferation by acting as a sponge for miR-9-5p and miR-338-3p and upregulating KLF5 and ADAM17 expression in pancreatic ductal adenocarcinoma.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-02-19 DOI:10.1186/s12935-025-03687-0

Kun-Lin Lee, Jun-Jen Liu, Wei-Jan Huang, Ching-Sheng Hung, Yu-Chih Liang

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引用次数: 0

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of solid tumor, and novel strategies must be developed for treating it. Previous studies predominantly utilized circular RNA (circRNA) expression plasmids incorporating Alu elements to facilitate the indirect expression of circRNA.

Methods: Public databases and bioinformatics tools were used to identify hsa_circ_0004781 that is highly expressed in PDAC and its potential microRNA (miRNA) targets and corresponding mRNA targets. Real hsa_circ_0004781, which is identical to the native form of hsa_circ_0004781 without any exogenous sequences, was prepared through in vitro transcription by using a ribozyme and ion-pair reversed-phase high-performance liquid chromatography (IP-RP HPLC). The biological functions of hsa_circ_0004781 were evaluated using loss-of-function and gain-of-function approaches with circRNA expression plasmids and real hsa_circ_0004781.

Results: Knockdown of hsa_circ_0004781 inhibited the proliferation and migration of PDAC cells, whereas its overexpression produced opposite effects. Hsa_circ_0004781 was identified as a sponge for miR-9-5p and miR-338-3p, and its expression was negatively correlated with that of these miRNAs. Among the targets of miR-9-5p and miR-338-3p, Kruppel-like factor 5 (KLF5) and a disintegrin and metalloproteinase domain 17 (ADAM17) were negatively correlated with survival in patients with PDAC and were inversely regulated by these miRNAs. Furthermore, real hsa_circ_0004781 exhibited the same effects as those of the circRNA expression plasmids.

Conclusions: This study is the first to use real circRNAs to validate results obtained using circRNA expression plasmids. The results suggest that hsa_circ_0004781 functions as an oncogene, promoting the proliferation of PDAC cells through the miR-9-5p/KLF5 and miR-338-3p/ADAM17 axes. Therefore, hsa_circ_0004781 might be a therapeutic target for PDAC.

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CircRNA hsa_circ_0004781在胰腺导管腺癌中作为miR-9-5p和miR-338-3p的海绵，上调KLF5和ADAM17的表达，从而促进细胞增殖。

背景：胰腺导管腺癌（Pancreatic ductal adenocarcinoma， PDAC）是侵袭性最强的实体肿瘤之一，必须发展新的治疗策略。先前的研究主要利用含有Alu元件的环状RNA （circRNA）表达质粒来促进circRNA的间接表达。方法：利用公共数据库和生物信息学工具鉴定PDAC中高表达的hsa_circ_0004781及其潜在的microRNA （miRNA）靶点和相应的mRNA靶点。采用核酶和离子对反相高效液相色谱法（IP-RP HPLC）体外转录，制备了与原hsa_circ_0004781完全相同的真实hsa_circ_0004781，不含外源序列。采用circRNA表达质粒和真实hsa_circ_0004781的功能丧失和功能获得方法评估hsa_circ_0004781的生物学功能。结果：低表达hsa_circ_0004781可抑制PDAC细胞的增殖和迁移，而过表达hsa_circ_0004781则相反。Hsa_circ_0004781被鉴定为miR-9-5p和miR-338-3p的“海绵”，其表达与这些mirna呈负相关。在miR-9-5p和miR-338-3p的靶点中，kruppel样因子5 （KLF5）和崩解素和金属蛋白酶结构域17 （ADAM17）与PDAC患者的生存呈负相关，并受这些mirna的负调控。此外，真实的hsa_circ_0004781表现出与circRNA表达质粒相同的效果。结论：本研究首次使用真实的circRNA来验证使用circRNA表达质粒获得的结果。结果表明，hsa_circ_0004781作为致癌基因，通过miR-9-5p/KLF5和miR-338-3p/ADAM17轴促进PDAC细胞的增殖。因此，hsa_circ_0004781可能是PDAC的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.