LncRNA PVT1 accelerates malignant phenotypes of bladder cancer cells by modulating miR-194-5p/BCLAF1 axis as a ceRNA.
LncRNA PVT1 accelerates malignant phenotypes of bladder cancer cells by modulating miR-194-5p/BCLAF1 axis as a ceRNA.
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LncRNA PVT1 通过调节 miR-194-5p/BCLAF1 轴作为 ceRNA 加速膀胱癌细胞的恶性表型
DOI：
10.18632/aging.202203
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发表时间：
2020-11-16
期刊：
影响因子：
--
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Chen M;Zhang R;Lu L;Du J;Chen C;Ding K;Wei X;Zhang G;Huang Y;Hou J
背景资料：大量研究表明，长链非编码RNA（lncRNA）参与了多种疾病的发生、发展，尤其是某些肿瘤的发生、发展。浆细胞瘤变异易位1基因（plasmacytoma variant translocation 1 gene，PVT 1）作为一种潜在的肿瘤生物标志物，与多种肿瘤的发生、发展密切相关。然而，PVT 1在膀胱癌中的内在和具体分子机制仍不清楚，这也是许多非编码RNA研究面临的困境。结果：我们的研究表明，PVT 1在膀胱癌标本和细胞系中表达明显升高。进一步的实验表明，PVT 1的敲低或过表达抑制或促进膀胱癌细胞的恶性表型和WNT/β-catenin信号传导。而miR-194- 5 p则相反，miR-194- 5 p可部分逆转恶性膀胱肿瘤细胞中PVT 1的功能。作为microRNA海绵，PVT 1积极促进b细胞淋巴瘤2相关转录因子1（BCLAF 1）的表达以海绵miR-194- 5 p，并随后增加膀胱癌细胞的恶性表型。因此，它具有致癌作用，而miR-194- 5 p具有相反的功能，并在膀胱癌发病机制中充当抗癌基因。结论：PVT 1-miR-194- 5 p-BCLAF 1轴参与膀胱癌的恶性进展和发展。实验表明，PVT 1对膀胱癌（BC）具有显著的调节作用，可作为BC患者的临床诊断标志物和治疗分子标志物。研究方法：采用定量逆转录PCR（RT-qPCR）检测膀胱癌标本及细胞系中PVT 1和miR-194- 5 p的相对表达水平。通过功能缺失和过表达等实验，探讨PVT 1和miR-194- 5 p对膀胱癌细胞增殖、迁移、凋亡和致瘤性的生物学效应。采用免疫共沉淀、蛋白质组学实验、双荧光素酶报告基因分析、蛋白质印迹等方法研究PVT 1在膀胱癌中的作用机制。
Background: Numerous studies proved that long non-coding RNA (lncRNA) is involved in the progression of multifarious diseases, especially in some carcinomas. As a potential tumor biomarker, plasmacytoma variant translocation 1 gene (PVT1) is involved in the development and progression of multifarious cancers. Nevertheless, the intrinsic and concrete molecular mechanism of PVT1 in bladder cancer still remained unclear, which is also the dilemma faced in many non-coding RNA studies. Results: Our research revealed that PVT1 was significantly higher expression in bladder carcinoma specimens and cell lines. Further experiments indicated that knockdown or overexpression of PVT1 restrained or promoted the malignant phenotype and WNT/β-catenin signaling in bladder cancer cells. Meanwhile miR-194-5p was in contrast and miR-194-5p could partially reverse the function of PVT1 in malignant bladder tumor cells. As a microRNA sponge, PVT1 actively promotes the expression of b-cells lymphoma-2-associated transcription factor 1 (BCLAF1) to sponge miR-194-5p and subsequently increases malignant phenotypes of bladder cancer cells. Therefore, it performs a carcinogenic effect and miR-194-5p as the opposite function, and serves as an antioncogene in the bladder carcinomas pathogenesis. Conclusion: PVT1-miR-194-5p-BCLAF1 axis is involved in the malignant progression and development of bladder carcinomas. Experiments revealed that PVT1 has a significant regulatory effect on bladder cancer (BC) and can be used as a clinical diagnostic marker and a therapeutic molecular marker for patients suffering from BC. Methods: In urothelial bladder carcinoma specimens and cell lines, the relative expression levels of PVT1 and miR-194-5p were detected by quantitative reverse transcription PCR (RT-qPCR). Through experiments such as loss-function and over-expression, the biological effects of PVT1 and miR-194-5p on the proliferation, migration, apoptosis and tumorigenicity were explored in bladder cancer cells. Co-immunoprecipitation, proteomics experiments, dual luciferase reporter gene analysis, western blot and other methods were adopted to investigate the PVT1 potential mechanism in bladder carcinomas.
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