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长链非编码RNA FER1L4通过海绵吸附miR-92a-3p和上调FBXW7来抑制前列腺癌进展。

Long non-coding RNA FER1L4 inhibits prostate cancer progression via sponging miR-92a-3p and upregulation of FBXW7.

作者信息

Huo Wei, Qi Fei, Wang Kaichen

机构信息

1Department of Urology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130001 People's Republic of China.

2Department of Operating Room, China-Japan Union Hospital, Jilin University, Changchun, 130001 People's Republic of China.

出版信息

Cancer Cell Int. 2020 Feb 28;20:64. doi: 10.1186/s12935-020-1143-0. eCollection 2020.

DOI:10.1186/s12935-020-1143-0
PMID:32140077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7049228/
Abstract

BACKGROUND

Dysregulation of long non-coding RNAs (lncRNAs) is involved in development of prostate cancer. However, the molecular mechanisms of many lncRNAs in prostate cancer have not been studied yet.

METHODS

The lncRNA Fer-1-like protein 4 (FER1L4) expression was explored in prostate tumors and normal prostate tissues by RT-qPCR and bioinformatic analysis. Overexpression of FER1L4 was performed to evaluate its role in prostate cancer cell proliferation and survival. The molecular mechanism of FER1L4 was investigated by dual luciferase reporter assay, RNA pull down assay, western blotting and RT-qPCR.

RESULTS

It was found that FER1L4 was lower in prostate cancer tissues than normal tissues. Higher expression of FER1L4 was associated with prostate cancer tissues of early stage (AJCC stage I/II). Overexpression of FER1L4 inhibited cell proliferation and promoted cell apoptosis in prostate cancer cells. Bioinformatic analysis, RT-qPCR, RNA pull down assay and dual luciferase assay showed that FER1L4 upregulated F-box/WD repeat-containing protein 7 (FBXW7) tumor suppressor via sponging miR-92a-3p. Silencing of FBXW7 reversed the cell phenotypes caused by FER1L4 overexpression in prostate cancer cells.

CONCLUSION

The data demonstrated that FER1L4, a downregulated lncRNA in prostate cancer, was pivotal for cell proliferation and survival of prostate cancer. The study provided new sights into understanding of the signaling network in prostate cancer and implied that FER1L4 might be a biomarker for patients with prostate cancer.

摘要

背景

长链非编码RNA（lncRNA）失调与前列腺癌的发生发展有关。然而，许多lncRNA在前列腺癌中的分子机制尚未得到研究。

方法

通过RT-qPCR和生物信息学分析，探究lncRNA Fer-1样蛋白4（FER1L4）在前列腺肿瘤组织和正常前列腺组织中的表达情况。进行FER1L4过表达实验，以评估其在前列腺癌细胞增殖和存活中的作用。通过双荧光素酶报告基因检测、RNA下拉实验、蛋白质免疫印迹法和RT-qPCR研究FER1L4的分子机制。

结果

发现前列腺癌组织中FER1L4的表达低于正常组织。FER1L4高表达与早期前列腺癌组织（美国癌症联合委员会分期I/II期）相关。FER1L4过表达抑制前列腺癌细胞增殖并促进细胞凋亡。生物信息学分析、RT-qPCR、RNA下拉实验和双荧光素酶检测表明，FER1L4通过吸附miR-92a-3p上调含F盒/ WD重复序列蛋白7（FBXW7）肿瘤抑制因子。FBXW7沉默逆转了FER1L4过表达在前列腺癌细胞中引起的细胞表型。

结论

数据表明，FER1L4作为前列腺癌中下调的lncRNA，对前列腺癌细胞的增殖和存活至关重要。该研究为理解前列腺癌的信号网络提供了新的视角，并暗示FER1L4可能是前列腺癌患者的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/5fac01e99040/12935_2020_1143_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/fa69290aab3a/12935_2020_1143_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/cde0c641008c/12935_2020_1143_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/c243178bd31e/12935_2020_1143_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/372fa3d6bed4/12935_2020_1143_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/e5e10fcc99f0/12935_2020_1143_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/955da56a53ee/12935_2020_1143_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/ff70a97184e5/12935_2020_1143_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/5fac01e99040/12935_2020_1143_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/fa69290aab3a/12935_2020_1143_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/cde0c641008c/12935_2020_1143_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/c243178bd31e/12935_2020_1143_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/372fa3d6bed4/12935_2020_1143_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/e5e10fcc99f0/12935_2020_1143_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/955da56a53ee/12935_2020_1143_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/ff70a97184e5/12935_2020_1143_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d8/7049228/5fac01e99040/12935_2020_1143_Fig8_HTML.jpg

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