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微小RNA-506通过抑制孤儿核受体NR4A1的表达来抑制结直肠癌的发展。

MiR-506 Suppresses Colorectal Cancer Development by Inhibiting Orphan Nuclear Receptor NR4A1 Expression.

作者信息

Huang Meihui, Xie Xina, Song Xuhong, Gu Songgang, Chang Xiaolan, Su Ting, Liang Bin, Huang Dongyang

机构信息

Department of Cell Biology and Genetics and Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou 515041, China.

Department of Pathology and Central Laboratory, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, China.

出版信息

J Cancer. 2019 Jun 9;10(15):3560-3570. doi: 10.7150/jca.28272. eCollection 2019.

DOI:10.7150/jca.28272
PMID:31293661
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6603418/
Abstract

NR4A1 acts as an oncogene and plays an important role in colorectal cancer development and progression, but little is known about the regulatory mechanism of NR4A1 expression. MicroRNA (miRNA) is involved in the progression of various tumors, affecting proliferation, apoptosis or migration. We aimed to elucidate whether miRNA regulates NR4A1 expression and determine its underlying significance in colorectal cancer. By using the TargetScan database, we identified a miR-506 binding site in the NR4A1 3'-UTR. Examination of colorectal cancer tissues and cells revealed that NR4A1 mRNA and protein were up-regulated, while miR-506 expression was down-regulated. Spearman correlation analysis revealed that expression of NR4A1 mRNA was negatively correlated with miR-506 levels in colorectal cancer tissue. Further studies indicated that miR-506 decreased NR4A1 expression through directly targeting the NR4A1 mRNA 3'-UTR. Functional experiments showed that rescue of NR4A1 expression in cells reversed the inhibitory effects of miR-506 on proliferation, migration and invasion of colorectal cancer cells. In conclusion, miR-506 acts as a tumor suppressor and inhibits proliferation, migration and invasion in colorectal cancer cells partly through decreasing NR4A1 expression.

摘要

NR4A1作为一种癌基因，在结直肠癌的发生和发展中起重要作用，但关于NR4A1表达的调控机制知之甚少。微小RNA（miRNA）参与各种肿瘤的进展，影响细胞增殖、凋亡或迁移。我们旨在阐明miRNA是否调节NR4A1表达，并确定其在结直肠癌中的潜在意义。通过使用TargetScan数据库，我们在NR4A1的3'-UTR中鉴定出一个miR-506结合位点。对结直肠癌组织和细胞的检测显示，NR4A1 mRNA和蛋白上调，而miR-506表达下调。Spearman相关性分析显示，结直肠癌组织中NR4A1 mRNA的表达与miR-506水平呈负相关。进一步研究表明，miR-506通过直接靶向NR4A1 mRNA的3'-UTR降低NR4A1表达。功能实验表明，细胞中NR4A1表达的恢复逆转了miR-506对结直肠癌细胞增殖、迁移和侵袭的抑制作用。总之，miR-506作为一种肿瘤抑制因子，部分通过降低NR4A1表达来抑制结直肠癌细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/f0244a6489a0/jcav10p3560g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/2552f186bb3a/jcav10p3560g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/add4416f34af/jcav10p3560g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/8aae1c160b4e/jcav10p3560g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/dd4ebd7766a6/jcav10p3560g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/92b2eb987630/jcav10p3560g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/3b1049b6e7e5/jcav10p3560g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/f0244a6489a0/jcav10p3560g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/2552f186bb3a/jcav10p3560g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/add4416f34af/jcav10p3560g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/8aae1c160b4e/jcav10p3560g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/dd4ebd7766a6/jcav10p3560g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/92b2eb987630/jcav10p3560g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/3b1049b6e7e5/jcav10p3560g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e046/6603418/f0244a6489a0/jcav10p3560g007.jpg

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