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HOXA11-AS 通过海绵吸附 miR-146b-5p 来上调 MMP16 表达,促进肾癌细胞的生长和侵袭。

HOXA11-AS promotes the growth and invasion of renal cancer by sponging miR-146b-5p to upregulate MMP16 expression.

机构信息

Department of Urology, Ninghai First Hospital, Zhejiang, China.

Department of Urology, Ninghai Hospital, Branch of Shanghai Tenth People's Hospital, Zhejiang, China.

出版信息

J Cell Physiol. 2018 Dec;233(12):9611-9619. doi: 10.1002/jcp.26864. Epub 2018 Jun 28.

DOI:10.1002/jcp.26864
PMID:29953617
Abstract

Recently, increasing studies showed that long noncoding RNAs (lncRNAs) play critical roles in tumor progression. However, the function and underlying mechanism of HOMEOBOX A11 antisense RNA (HOXA11-AS) on renal cancer remain unclear. In the current study, our data showed that the expression of HOXA11-AS was significantly upregulated in clear cell renal cell carcinoma (ccRCC) tissues and cell lines. High HOXA11-AS expression was associated with the advanced clinical stage, tumor stage, and lymph node metastasis. Function assays showed that HOXA11-AS inhibition significantly suppressed renal cancer cells growth, invasion, and ETM phenotype. In addition, underlying mechanism revealed that HOXA11-AS could act as a competing endogenous RNA (ceRNA) that repressed miR-146b-5p expression, which regulated its downstream target MMP16 in renal cancer. Taken together, our findings suggested that HOXA11-AS could promote renal cancer cells growth and invasion by modulating miR-146b-5p-MMP16 axis. Thus, our findings suggested that HOXA11-AS could serve as potential therapeutic target for the treatment of renal cancer.

摘要

最近,越来越多的研究表明长非编码 RNA(lncRNA)在肿瘤进展中发挥着关键作用。然而,HOXA11 反义 RNA(HOXA11-AS)在肾细胞癌中的功能和潜在机制尚不清楚。在本研究中,我们的数据表明 HOXA11-AS 在透明细胞肾细胞癌(ccRCC)组织和细胞系中的表达显著上调。高 HOXA11-AS 表达与晚期临床分期、肿瘤分期和淋巴结转移有关。功能分析表明,HOXA11-AS 抑制显著抑制肾癌细胞的生长、侵袭和上皮间质转化表型。此外,潜在机制表明 HOXA11-AS 可以作为竞争性内源性 RNA(ceRNA),抑制 miR-146b-5p 的表达,从而调节肾癌细胞中的下游靶基因 MMP16。综上所述,我们的研究结果表明,HOXA11-AS 可以通过调节 miR-146b-5p-MMP16 轴促进肾癌细胞的生长和侵袭。因此,我们的研究结果表明,HOXA11-AS 可以作为治疗肾细胞癌的潜在治疗靶点。

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