Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis.
Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis.
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NF-KappaB 上调的环状 RNA CircNOLC1 通过 miR-647/PAQR4 轴促进前列腺癌的进展
DOI：
10.3389/fcell.2020.624764
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发表时间：
2020
影响因子：
5.5
通讯作者：
Mao X
中科院分区：
文献类型：
--
作者：
Chen W;Cen S;Zhou X;Yang T;Wu K;Zou L;Luo J;Li C;Lv D;Mao X
研究背景：CircRNAs在肿瘤生物学中发挥着重要作用。然而，它们在前列腺癌(PCa)中的作用在很大程度上仍不清楚。方法应用CircRNA芯片技术对前列腺癌永生细胞株RWPE1和PCa细胞株DU145、PC3、LNCaP、C4-2和22Rv1进行检测。结合PCa组织中上调的CircRNAs，通过qRT-PCR和FISH验证了CircNOLC1在PCa细胞和组织中的表达。采用Sanger测序、放线菌素D、gDNA及cDNAs、RNase R等方法分析CircNOLC1基因的环状特征。通过CCK-8、集落形成、跨孔迁移实验和小鼠异种移植模型，评估了CircNOLC1基因敲除和过表达后PCA细胞的功能。利用RNA下拉、荧光素酶报告实验、荧光原位杂交和芯片等方法进一步阐明了CircNOLC1的作用机制。结果CircNOLC1在PCa细胞和组织中高表达，并且比线性NOLC1mRNA更稳定。CircNOLC1在体内外均能促进PCa细胞的增殖和迁移。此外，我们还发现，CircNOLC1可以通过海绵作用miR-647上调PAQR4的表达，从而激活PI3K/Akt通路。此外，核因子-kappaB可与NOLC1启动子结合，上调NOLC1和CircNOLC1的表达。结论转录因子NF-kappaB上调的CircNOLC1通过miR-647/PAQR4轴促进PCa的进展，CircNOLC1是治疗PCa的潜在生物标志物和靶点。
Background CircRNAs recently have shown critical roles in tumor biology. However, their roles in prostate cancer (PCa) remains largely unclear. Methods CircRNA microarrays were performed in immortal prostate cell line RWPE1 and PCa cell lines as DU145, PC3, LNCaP, C4-2, and 22RV1. Combined with upregulated circRNAs in PCa tissues, circNOLC1 expression was validated in PCa cells and tissues via qRT-PCR and FISH. Sanger sequencing, actinomycin D, gDNA, and cDNA, RNase R assays were used to assess the circular characteristics of circNOLC1. CCK-8, colony formation, transwell migration assays, and mice xenograft models were conducted to evaluate the functions of PCa cells after circNOLC1 knockdown and overexpression. RNA pulldown, luciferase reporter assay, FISH (fluorescence in situ hybridization), and CHIP were utilized to illustrate the further mechanisms of circNOLC1. Results Our research indicated that circNOLC1 was overexpressed in PCa cells and tissues, and circNOLC1 was more stable than linear NOLC1 mRNA. CircNOLC1 promoted PCa cells proliferation and migration in vitro and vivo. Additionally, we found that circNOLC1 could upregulate PAQR4 expression by sponging miR-647, leading to the activation of PI3K/Akt pathway. Moreover, NF-kappaB was identified to bind to the NOLC1 promoter sites and upregulated both NOLC1 and circNOLC1 expression. Conclusion CircNOLC1, elevated by transcription factor NF-kappaB, promotes PCa progression via a miR-647/PAQR4 axis, and circNOLC1 is a potential biomarker and target for PCa treatment.
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