LncRNA VPS9D1-AS1 regulates miR-187-3p/fibroblast growth factor receptor-like 1 axis to promote proliferation, migration, and invasion of prostate cancer cells.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-09-01 DOI:10.4103/cjop.CJOP-D-23-00054

Chenguang Wu, Jian Chen, Dong Wang

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引用次数: 0

Abstract

The morbidity and mortality of prostate cancer are increasing year by year, and the survival rate of prostate cancer patients after treatment is low. Therefore, investigating the molecular mechanism underlying prostate cancer is crucial for developing effective treatments. Recent studies have shown the important role of long-chain non-coding RNAs (lncRNAs) in tumorigenesis. VPS9D1-AS1 can modulate the progression of multiple cancers, but its molecular action mechanism in prostate cancer remains unknown. This study, therefore, intended to investigate the regulatory mechanism of VPS9D1-AS1 in prostate cancer. First, differentially expressed lncRNAs in prostate cancer were identified through bioinformatics approaches. The target lncRNA for the study was determined by reviewing the relevant literature and its downstream miRNA/mRNA axis was uncovered. Then, quantitative reverse transcription polymerase chain reaction was introduced to assess the expression of VPS9D1-AS1, miR-187-3p, and fibroblast growth factor receptor-like 1 (FGFRL1) at a cellular level, and Western blot was conducted to assess the protein level of FGFRL1 in cells. The results indicated that VPS9D1-AS1 and FGFRL1 were highly expressed in prostate cancer while miR-187-3p was less expressed. Besides, MTT, colony formation, wound healing, and cell invasion assays showed that silencing VPS9D1-AS1 inhibited the viability, migration ability, and invasion ability of prostate cancer cells. Dual-luciferase assay and RNA binding protein immunoprecipitation assay were performed to explore the interplay of miR-187-3p and VPS9D1-AS1 or FGFRL1. The results showed that VPS9D1-AS1 could sponge miR-187-3p, and FGFRL1 could serve as a direct target of miR-187-3p. Moreover, combined with the results of the rescue experiment, VPS9D1-AS1 was found to upregulate FGFRL1 by competitively sponging miR-187-3p to accelerate the malignant behaviors of prostate cancer cells. In conclusion, VPS9D1-AS1 could promote the phenotype progression of prostate cancer cells through targeting the miR-187-3p/FGFRL1 axis, and it has the potential to be a target for prostate cancer patients.

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LncRNA VPS9D1-AS1调节miR-187-3p/成纤维细胞生长因子受体样1轴，以促进前列腺癌症细胞的增殖、迁移和侵袭。

前列腺癌症的发病率和死亡率逐年上升，癌症患者治疗后生存率较低。因此，研究癌症的分子机制对于开发有效的治疗方法至关重要。最近的研究表明，长链非编码RNA（lncRNA）在肿瘤发生中发挥着重要作用。VPS9D1-AS1可以调节多种癌症的进展，但其在前列腺癌症中的分子作用机制尚不清楚。因此，本研究旨在研究VPS9D1-AS1在前列腺癌症中的调节机制。首先，通过生物信息学方法鉴定了前列腺癌症中差异表达的lncRNA。通过查阅相关文献确定了本研究的靶lncRNA，并揭示了其下游miRNA/mRNA轴。然后，引入定量逆转录聚合酶链反应以在细胞水平上评估VPS9D1-AS1、miR-187-3p和成纤维细胞生长因子受体样1（FGFRL1）的表达，并进行蛋白质印迹以评估细胞中FGFRL1的蛋白质水平。结果表明，VPS9D1-AS1和FGFRL1在前列腺癌症中高表达，而miR-187-3p表达较少。此外，MTT、集落形成、伤口愈合和细胞侵袭试验表明，沉默VPS9D1-AS1抑制了前列腺癌症细胞的生存能力、迁移能力和侵袭能力。进行双荧光素酶测定和RNA结合蛋白免疫沉淀测定，以探索miR-187-3p与VPS9D1-AS1或FGFRL1的相互作用。结果表明，VPS9D1-AS1可以吸附miR-187-3p，FGFRL1可以作为miR-187-3 p的直接靶标。此外，结合拯救实验的结果，发现VPS9D1-AS1通过竞争性吸附miR-187-3p来上调FGFRL1，以加速前列腺癌症细胞的恶性行为。总之，VPS9D1-AS1可以通过靶向miR-187-3p/FGFRL1轴来促进前列腺癌症细胞的表型进展，具有成为前列腺癌症患者靶点的潜力。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.