miR-1-3p、miR-143-3p和miR-145-5p与Gleason 3+4前列腺癌症骨转移和参与LASP1调节的相关性鉴定

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Hongwei Guo , Jinlong Zhao , Xinjun Li , Feifei Sun , Yiming Qin , Xiaorong Yang , Xueting Xiong , Qianshuo Yin , Xueli Wang , Lin Gao , Meng Jiao , Jing Hu , Bo Han
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引用次数: 1

摘要

格里森评分(GS)3+4前列腺癌症(PCa)在临床过程和分子特征上是异质性的。GS3+4的惰性和侵袭性前列腺癌的风险分层至关重要,尤其是那些有骨转移(BM)潜力的前列腺癌。使用基于微阵列的微小RNA(miRNA)图谱对8例患有或不患有BM的前列腺癌病例进行分析,以筛选与BM相关的候选miRNA。使用Transwell和MTS分析来表征miRNA和靶基因LASP1的功能。利用RT-qPCR和免疫组织化学分析来说明309例中国前列腺癌患者队列中miRNA和靶基因的临床意义。在目前的研究中,我们发现miR-1-3p、miR-143-3p和miR-145-5p与GS 3+4 PCa的BM相关。通过功能实验,我们发现miR-1-3p/143–3p/145–5p在体外促进前列腺癌的增殖和迁移。LASP1被预测为这三种miRNA的共同靶标,这通过荧光素酶测定得到了进一步证实。免疫组化显示LASP1的过度表达与较高的GS、较高的病理分期和转移的存在相关。siRNA敲低LASP1显著抑制增殖和迁移,而过表达LASP1促进增殖和迁移。生物信息学分析揭示了Wnt信号通路参与LASP1介导的功能。LASP1可能通过与β-连环蛋白相互作用来激活Wnt信号传导。总之,我们认为miR-1-3p/143–3p/145–5p与Gleason 3+4 PCa的BM相关。LASP1是这些miRNA的共同靶点,可能通过与β-连环蛋白相互作用激活Wnt信号传导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation

Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143–3p and miR-145–5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143–3p/145–5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with β-catenin. In all, we suggest that miR-1-3p/143–3p/145–5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with β-catenin.

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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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