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长链非编码 RNA CASC9 通过作为 miR-497-5p 的 ceRNA 来上调 CCND1 的表达,促进胰腺癌的进展。

Long noncoding RNA CASC9 promotes pancreatic cancer progression by acting as a ceRNA of miR-497-5p to upregulate expression of CCND1.

机构信息

Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Environ Toxicol. 2023 Jun;38(6):1251-1264. doi: 10.1002/tox.23761. Epub 2023 Mar 22.

Abstract

BACKGROUND

Pancreatic cancer (PC) is an aggressive malignancy with poor prognosis. Accumulating studies have showed that long non-coding RNA (lncRNA) is a crucial regulator in various tumorigenesis and progression including PC. This research aims to explore the roles and molecular mechanism of lncRNA cancer susceptibility candidate 9 (CASC9) in PC.

METHODS

The expression levels of lncRNA CASC9 and miR-497-5p were evaluated in PC tissues and paired adjacent healthy tissues by quantitative real-time PCR. PC cell lines were transfected with lentivirus targeting lncRNA CASC9, and cells proliferation, migration and invasion tests were conducted. Dual luciferase reporter assays were also carried out to explore the relationship between lncRNA CASC9, miR-497-5p and Cyclin D1 (CCND1).

RESULTS

LncRNA CASC9 was significantly up-regulated in PC tissues, while miR-497-5p expression was down-regulated. Down-regulation of lncRNA CASC9 in PC cells can significantly suppress the cell aggressiveness both in vitro and in vivo; moreover, knock-down of miR-497-5p could neutralize this impact. Additionally, the luciferase activity assay has assured that CCND1 was a downstream target of miR-497-5p.

CONCLUSION

LncRNA CASC9 can promote the PC progression by modulating miR-497-5p/CCND1 axis, which is potential target for PC treatment.

摘要

背景

胰腺癌(PC)是一种预后不良的侵袭性恶性肿瘤。越来越多的研究表明,长链非编码 RNA(lncRNA)是包括 PC 在内的多种肿瘤发生和进展的关键调节因子。本研究旨在探讨 lncRNA 癌症易感性候选基因 9(CASC9)在 PC 中的作用和分子机制。

方法

通过实时定量 PCR 检测 PC 组织和配对的相邻正常组织中 lncRNA CASC9 和 miR-497-5p 的表达水平。用靶向 lncRNA CASC9 的慢病毒转染 PC 细胞系,并进行细胞增殖、迁移和侵袭试验。双荧光素酶报告基因实验也用于探索 lncRNA CASC9、miR-497-5p 和细胞周期蛋白 D1(CCND1)之间的关系。

结果

lncRNA CASC9 在 PC 组织中显著上调,而 miR-497-5p 的表达则下调。PC 细胞中 lncRNA CASC9 的下调可显著抑制体外和体内的细胞侵袭性;此外,miR-497-5p 的敲低可中和这种影响。此外,荧光素酶活性测定证实 CCND1 是 miR-497-5p 的下游靶标。

结论

lncRNA CASC9 可通过调节 miR-497-5p/CCND1 轴促进 PC 的进展,这可能是 PC 治疗的潜在靶点。

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