Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification

Chen，Erbao1,2; Yi，Jing1; Ren，Qingqi1; Mi，Yuanna1; Gan，Zhe1; Liu，Jikui1

2022

10.1155/2022/7853168

Evidence-based Complementary and Alternative Medicine   Impact Factor & Quartile

1741-427X

1741-4288

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and more prevalent among males than females. However, the biological role of enzyme 5α-reductase (SRD5A3), which plays a critical role in the androgen receptor signaling pathway during HCC development, remains poorly understood. Methods. ONCOMINE, GEPIA, UALCAN, and Kaplan-Meier Plotter were used to analyze the expression and prognostic value of SRD5A3 in HCC. STRING and Metascape were applied to analyze potential target and molecular pathways underlying SRD5A3 in HCC. A real-time quantitative reverse transcription-polymerase chain reaction was used to validate the downstream target expression of SRD5A3. Results. The expression of SRD5A3 was significantly overexpressed in HCC tissues compared with normal tissues, while the expression of SRD5A1 and SRD5A2 were downregulated in multiple public datasets. It may be that the low methylation of the SRD5A3 promoter leads to its overexpression. The level of SRD5A3 tended to be higher expressed in clinical samples with advanced stage and positive node metastasis. Furthermore, the patients with higher SRD5A3 were remarkably associated with poorer overall survival and disease-free survival in the TCGA data. In addition, the increased mRNA expression of SRD5A3 could predict poorer overall survival in Kaplan-Meier Plotter database including different patient cohorts. Moreover, HCC patients with higher level of SRD5A3 had significantly shorter recurrence-free survival, progression-free survival, and disease-specific survival. Furthermore, enrichment analysis demonstrated that multiple processes, such as steroid hormone biosynthesis, lipid biosynthetic process, and androgen metabolic process, were affected by SRD5A1-3 alterations. In vitro experiments showed that the expression of SRD5A3 was increased in HCC tissues than that in adjacent tissues. SRD5A3 silencing promoted the expression of DOLK in two HCC cell lines. Conclusions. This study identified SRD5A3/DOLK as a novel axis to regulate HCC development.

SCI

English

Others

[SZSM201612021] ; [2020M682779] ; [2021T140295]

Integrative & Complementary Medicine

Integrative & Complementary Medicine

WOS:000864466900011

HINDAWI LTD

2-s2.0-85138896369

Scopus

1.Department of Hepatobiliary and Pancreatic Surgery,Peking University Shenzhen Hospital,Shenzhen,Guangdong,518036,China
2.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China

Chen，Erbao,Yi，Jing,Ren，Qingqi,et al. Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification[J]. Evidence-based Complementary and Alternative Medicine,2022,2022.

Chen，Erbao,Yi，Jing,Ren，Qingqi,Mi，Yuanna,Gan，Zhe,&Liu，Jikui.(2022).Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification.Evidence-based Complementary and Alternative Medicine,2022.

Chen，Erbao,et al."Overexpression of SRD5A3 in Hepatocellular Carcinoma and Its Molecular Mechanism: A Study of Bioinformatics Exploration Analysis with Experimental Verification".Evidence-based Complementary and Alternative Medicine 2022(2022).