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类固醇 5α-还原酶 3(SRD5A3)促进人肝癌(HCC)的肿瘤生长并预测不良预后。

Steroid 5 alpha-reductase 3 (SRD5A3) promotes tumor growth and predicts poor survival of human hepatocellular carcinoma (HCC).

机构信息

Department of Interventional Radiology, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.

PET/CT Center, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou 515041, Guangdong, China.

出版信息

Aging (Albany NY). 2020 Nov 20;12(24):25395-25411. doi: 10.18632/aging.104142.

DOI:10.18632/aging.104142
PMID:33229626
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7803539/
Abstract

Steroid 5 alpha-reductase 3 (SRD5A3) is an important molecule in glycosylation metabolism and steroid hormone formation. It is differentially expressed in human fetal liver, endometrial cancer and prostate cancer; however, its prognostic value and biological function in hepatocellular carcinoma (HCC) remain unclear. Here, bioinformatics analysis was employed to explore the expression and prognostic significance of SRD5A3 in various cancers including HCC. Additionally, clinical specimens of HCC were applied to analyze the expression of SRD5A3. SRD5A3-underexpressed HCC cell lines were established to test the effect of SRD5A3 on cell proliferation in and . We found that the elevated expression of SRD5A3 was common in many cancers with poor prognosis. Moreover, public datasets and our specimens revealed that SRD5A3 was also upregulated in HCC tissues and associated with clinical stage and patient's gender. Kaplan-Meier survival analysis showed that higher SRD5A3 level predicted poor overall survival, progression-free survival, relapse-free survival and disease specific survival in HCC patients. Further experiments showed that the lack of SRD5A3 inhibited the growth of HCC. Collectively, these findings indicate that SRD5A3 functions as an oncogene and might serve as a potential biomarker for prognosis and a therapeutic target for HCC.

摘要

5α-还原酶 3(SRD5A3)是糖基化代谢和甾体激素形成中的一个重要分子。它在人胎肝、子宫内膜癌和前列腺癌中差异表达;然而,其在肝细胞癌(HCC)中的预后价值和生物学功能尚不清楚。本研究通过生物信息学分析探讨了 SRD5A3 在包括 HCC 在内的多种癌症中的表达和预后意义。此外,还应用 HCC 的临床标本分析了 SRD5A3 的表达。建立了 SRD5A3 低表达 HCC 细胞系,以检测 SRD5A3 对细胞增殖的影响。我们发现,SRD5A3 的高表达在许多预后不良的癌症中很常见。此外,公共数据集和我们的标本表明,SRD5A3 在 HCC 组织中也上调,并与临床分期和患者性别相关。Kaplan-Meier 生存分析显示,HCC 患者中 SRD5A3 水平较高预示着总生存期、无进展生存期、无复发生存期和疾病特异性生存期较差。进一步的实验表明,缺乏 SRD5A3 抑制了 HCC 的生长。总之,这些发现表明 SRD5A3 作为一种癌基因发挥作用,可能成为 HCC 预后的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/cf0cf264f4b5/aging-12-104142-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/f0cbb223e0ea/aging-12-104142-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/b85989137228/aging-12-104142-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/b07b7517c6a7/aging-12-104142-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/fee8080c3e25/aging-12-104142-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/5dc637363502/aging-12-104142-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/cf0cf264f4b5/aging-12-104142-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/f0cbb223e0ea/aging-12-104142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/89f2549540a0/aging-12-104142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/beea69c19ad8/aging-12-104142-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/b85989137228/aging-12-104142-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/302846fb08cb/aging-12-104142-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/b07b7517c6a7/aging-12-104142-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/fee8080c3e25/aging-12-104142-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ef/7803539/5dc637363502/aging-12-104142-g008.jpg
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