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沉默的长链非编码RNA SNHG14通过调控微小RNA-211-3p/内皮抑素1轴抑制膀胱癌细胞的生物学行为。

Silenced lncRNA SNHG14 restrains the biological behaviors of bladder cancer cells via regulating microRNA-211-3p/ESM1 axis.

作者信息

Feng Rui, Li Zhongxing, Wang Xing, Ge Guangcheng, Jia Yuejun, Wu Dan, Ji Yali, Wang Chenghao

机构信息

Department of Urology, Zhenjiang Hospital of Chinese Traditional And Western Medicine, 18 Tuanshan Road, Zhenjiang, Jiangsu, 212002, China.

出版信息

Cancer Cell Int. 2021 Jan 22;21(1):67. doi: 10.1186/s12935-020-01717-7.

Abstract

BACKGROUND

Bladder cancer (BCa) is a malignant tumor that occurs on the mucosa of the bladder, in which dysregulated long non-coding RNAs (lncRNAs) are involved. This study investigated the effect of lncRNA small nucleolar RNA host gene 1 (SNHG14) on the biological characteristics of BCa cells from microRNA (miR)-211-3p/ESM1 signaling axis.

METHODS

BCa tissues and the matched normal tissues were collected to test SNHG14, miR-211-3p and ESM1 levels. SNHG14, miR-211-3p and ESM1 levels in BCa cell lines (T24, 5637, UMUC-3 and EJ) and normal bladder epithelial cells SV-HVC-1 were detected for screening the cell lines for follow-up experiments. T24 and UMUC-3 cells were transfected with different plasmids of SNHG14, miR-211-3p or ESM1 to observe the biological characteristics of BCa cells by MTT, colony formation, Transwell assays and flow cytometry. Tumor xenograft was implemented to inspect tumor growth in vivo. The targeting relationships of SNHG14, miR-211-3p and ESM1 were verified by bioinformatics software, RNA pull down assay and luciferase reporter assay.

RESULTS

Enhanced SNHG14, ESM1 and suppressed miR-211-3p were found in BCa tissues and cells. SNHG14 up-regulated ESM1 via competitive binding with miR-211-3p. Decreased SNHG14 or up-regulated miR-211-3p depressed cell cycle entry, colony formation, invasion, migration and proliferation abilities, and facilitated apoptosis of BCa cells. Decreased SNHG14 or up-regulated miR-211-3p reduced the tumor volume and weight of nude mice with BCa, as well as promoted apoptosis and restrained proliferation of tumor cells. miR-211-3p inhibition or ESM1 overexpression reversed the effects of down-regulation of SNHG14 on BCa, and miR-211-3p up-regulation or ESM1 downregulation reversed the effect of SNHG14 overexpression on BCa. SNHG14 targeted miR-211-3p to regulate ESM1 expression.

CONCLUSION

Our study highlights that silenced SNHG14 or elevated miR-211-3p represses the tumorigenic ability of BCa cells, which may be linked to ESM1 knockdown.

摘要

背景

膀胱癌(BCa)是一种发生于膀胱黏膜的恶性肿瘤,其中长链非编码RNA(lncRNA)表达失调。本研究从微小RNA(miR)-211-3p/内皮抑素1(ESM1)信号轴探讨lncRNA小核仁RNA宿主基因1(SNHG14)对BCa细胞生物学特性的影响。

方法

收集BCa组织及其配对的正常组织以检测SNHG14、miR-211-3p和ESM1水平。检测BCa细胞系(T24、5637、UMUC-3和EJ)及正常膀胱上皮细胞SV-HVC-1中SNHG14、miR-211-3p和ESM1水平,以筛选用于后续实验的细胞系。用不同的SNHG14、miR-211-3p或ESM1质粒转染T24和UMUC-3细胞,通过MTT法、集落形成实验、Transwell实验和流式细胞术观察BCa细胞的生物学特性。进行肿瘤异种移植以检测体内肿瘤生长情况。通过生物信息学软件、RNA下拉实验和荧光素酶报告基因实验验证SNHG14、miR-211-3p和ESM1的靶向关系。

结果

在BCa组织和细胞中发现SNHG14和ESM1表达增强,miR-211-3p表达受到抑制。SNHG14通过与miR-211-3p竞争性结合上调ESM1。SNHG14表达降低或miR-211-3p表达上调会抑制细胞周期进程、集落形成、侵袭、迁移和增殖能力,并促进BCa细胞凋亡。SNHG14表达降低或miR-211-3p表达上调会减小BCa裸鼠的肿瘤体积和重量,同时促进肿瘤细胞凋亡并抑制其增殖。抑制miR-211-3p或过表达ESM1可逆转SNHG14下调对BCa的影响,上调miR-211-3p或下调ESM1可逆转SNHG14过表达对BCa的影响。SNHG14靶向miR-211-3p以调节ESM1表达。

结论

我们的研究表明,沉默SNHG14或升高miR-211-3p可抑制BCa细胞的致瘤能力,这可能与ESM1表达降低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db5/7821404/a0cc3f54595a/12935_2020_1717_Fig1_HTML.jpg

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