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长链非编码RNA TMEM147-AS1/miR-133b/ZNF587轴调控瓦博格效应并促进前列腺癌侵袭与增殖。

The long non-sacoding RNA TMEM147-AS1/miR-133b/ZNF587 axis regulates the Warburg effect and promotes prostatic carcinoma invasion and proliferation.

作者信息

Wu Tao, Han Niwei, Zhao Changyong, Huang Xiang, Su Peng, Li Xiaoguang

机构信息

Department of Urology, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Department of Laboratory Medicine, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

出版信息

J Gene Med. 2022 Nov;24(11):e3453. doi: 10.1002/jgm.3453. Epub 2022 Oct 17.

Abstract

BACKGROUND

The Warburg effect is a characteristic tumor cell behavior regarded as one of the cancer hallmarks and promotes tumor progression by promoting glucose uptake and lactate production. Long non-coding RNAs (lncRNAs) had been reported to emerge as a vital function in cancer development. The present research is designed to investigate the underlying molecular mechanism of lncRNA TMEM147 antisense RNA 1 (TMEM147-AS1) on aerobic glycolysis in prostatic carcinoma.

METHODS

lncRNA TMEM147-AS1, miR-133b and ZNF587 levels in prostatic carcinoma tissues and cells were detected by a polymerase chain reaction or western blot assays. Cell viability or invasion was determined by Edu (i.e. 5-ethynyl-2'-deoxyuridine), MTT (i.e. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) or transwell assays. Hematoxylin and eosin and immunohistochemical staining were applied for histopathological examination. Tumor xenograft model was employed to investigate tumor growth in vivo. The combinative relationship between TMEM147-AS1 or ZNF587 and miR-133b was confirmed by a luciferase reporter assay.

RESULTS

TMEM147-AS1 and ZNF587 were up-regulated in prostatic carcinoma tissues and cells. Knockdown of TMEM147-AS1 or ZNF587 within prostate cancer cells significantly restrained cell viability, invasion and aerobic glycolysis in vitro and suppressed the neoplasia of prostatic carcinoma in vivo. miR-133b was directly targeted in both TMEM147-AS1 and ZNF587. Overexpression of miR-133b restrained prostate cancer cell viability, invasion and aerobic glycolysis. TMEM147-AS1 competitively targeted miR-133b, therefore counteracting miR-133b-mediated repression on ZNF587.

CONCLUSIONS

TMEM147-AS1 plays a tumor-promoting action in prostatic carcinoma aerobic glycolysis via affecting the miR-133b/ZNF587 axis, therefore regulating prostatic carcinoma cells invasion and proliferation. These outcomes implied that TMEM147-AS1 could be an effective treatment strategy for further study of prostatic carcinoma.

摘要

背景

瓦伯格效应是一种特征性的肿瘤细胞行为,被视为癌症标志之一,通过促进葡萄糖摄取和乳酸生成来促进肿瘤进展。据报道,长链非编码RNA(lncRNA)在癌症发展中发挥着重要作用。本研究旨在探讨lncRNA TMEM147反义RNA 1(TMEM147-AS1)对前列腺癌有氧糖酵解的潜在分子机制。

方法

采用聚合酶链反应或蛋白质免疫印迹法检测前列腺癌组织和细胞中lncRNA TMEM147-AS1、miR-133b和ZNF587的水平。通过Edu(即5-乙炔基-2'-脱氧尿苷)、MTT(即3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐)或Transwell实验测定细胞活力或侵袭能力。应用苏木精-伊红染色和免疫组织化学染色进行组织病理学检查。采用肿瘤异种移植模型研究体内肿瘤生长情况。通过荧光素酶报告基因实验证实TMEM147-AS1或ZNF587与miR-133b之间的结合关系。

结果

TMEM147-AS1和ZNF587在前列腺癌组织和细胞中上调。敲低前列腺癌细胞中的TMEM147-AS1或ZNF587可显著抑制体外细胞活力、侵袭和有氧糖酵解,并抑制体内前列腺癌的形成。miR-133b是TMEM147-AS1和ZNF587的直接靶点。miR-133b的过表达抑制前列腺癌细胞活力、侵袭和有氧糖酵解。TMEM147-AS1竞争性靶向miR-133b,从而抵消miR-133b介导的对ZNF587的抑制作用。

结论

TMEM147-AS1通过影响miR-133b/ZNF587轴在前列腺癌有氧糖酵解中发挥促肿瘤作用,从而调节前列腺癌细胞的侵袭和增殖。这些结果表明,TMEM147-AS1可能是进一步研究前列腺癌的有效治疗策略。

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