Research Paper Volume 12, Issue 24 pp 25395—25411
Steroid 5 alpha-reductase 3 (SRD5A3) promotes tumor growth and predicts poor survival of human hepatocellular carcinoma (HCC)
- 1 Department of Interventional Radiology, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China
- 2 PET/CT Center, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou 515041, Guangdong, China
- 3 Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, China
- 4 Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China
- 5 The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China
Received: June 25, 2020 Accepted: September 5, 2020 Published: November 20, 2020https://doi.org/10.18632/aging.104142
How to Cite
Copyright: © 2020 Mai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 in vitro and in vivo. 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.
ADK: adenosine kinase; AR: androgen receptor; BRCA: breast invasive carcinoma; CCK-8: Cell counting Kit-8; DHT: dihydrotestosterone; DNM3: Dynamin 3; DSS: disease specific survival; GEO: Gene Expression Omnibus; GBM: glioblastoma multiforme; HCC: hepatocellular carcinoma; HGF: hepatocyte growth factor; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LGG: brain lower grade glioma; NAFLD: nonalcoholic fatty liver disease; OS: overall survival; peri-HCC: corresponding adjacent non-HCC liver; PFS: progression-free survival; qRT-PCR: quantitative reverse-transcription polymerase chain reaction; RFS: relapse-free survival; sh-NC: control vector; sh-SRD5A3: SRD5A3 shRNA; SKCM: skin cutaneous melanoma; SRD5A1: steroid 5 alpha-reductase 1; SRD5A2: steroid 5 alpha-reductase 2; SRD5A3: steroid 5 alpha-reductase 3; TACE: transarterial chemoembolization; TCGA: The Cancer Genome Atlas; THCA: thyroid carcinoma; UVM: uveal melanoma.