An integrated analysis of dysregulated SCD1 in human cancers and functional verification of miR-181a-5p/SCD1 axis in esophageal squamous cell carcinoma

Bing-Yen Wang; Yuan-Yen Chang; Li-Yen Shiu; Yi-Ju Lee; Yu-Wei Lin; Yu-Shen Hsu; Hsin-Ting Tsai; Sung-Po Hsu; Li-Jen Su; Meng-Hsiu Tsai; Jing-Hong Xiao; Jer-An Lin; Chang-Han Chen

doi:10.1016/j.csbj.2023.08.009

An integrated analysis of dysregulated SCD1 in human cancers and functional verification of miR-181a-5p/SCD1 axis in esophageal squamous cell carcinoma

Comput Struct Biotechnol J. 2023 Aug 16:21:4030-4043. doi: 10.1016/j.csbj.2023.08.009. eCollection 2023.

Authors

Bing-Yen Wang^{1

2

3

4

5

6}, Yuan-Yen Chang⁷, Li-Yen Shiu^{8

9}, Yi-Ju Lee^{10

11}, Yu-Wei Lin¹¹, Yu-Shen Hsu¹¹, Hsin-Ting Tsai¹², Sung-Po Hsu^{13

14}, Li-Jen Su¹⁵, Meng-Hsiu Tsai¹⁵, Jing-Hong Xiao¹⁵, Jer-An Lin^{16

17}, Chang-Han Chen^{18

12

19

11}

Affiliations

¹ Division of Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Taiwan.
² Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan.
³ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁴ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁵ School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ Center for General Education, Ming Dao University, Changhua, Taiwan.
⁷ Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University, and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁸ Cell Therapy Center, E-Da cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
⁹ Cell Therapy and Research Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
¹⁰ Immunology Research Center, Chung Shan Medical University, Taichung, Taiwan.
¹¹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
¹² Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
¹³ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹⁴ Department of Physiology, School of Medicine, Taipei, Taiwan.
¹⁵ Department of Biomedical Sciences and Engineering, Education and Research Center for Technology Assisted Substance Abuse Prevention and Management, and Core Facilities for High Throughput Experimental Analysis, National Central University, Taoyuan County, Taiwan.
¹⁶ Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
¹⁷ Graduate Institute of Food Safety, National Chung Hsing University, Taichung, Taiwan.
¹⁸ Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, Taiwan.
¹⁹ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.

Abstract

Esophageal squamous cell carcinoma (ESCC), one of the most lethal cancers, has become a global health issue. Stearoyl-coA desaturase 1 (SCD1) has been demonstrated to play a crucial role in human cancers. However, pan-cancer analysis has revealed little evidence to date. In the current study, we systematically inspected the expression patterns and potential clinical outcomes of SCD1 in multiple human cancers. SCD1 was dysregulated in several types of cancers, and its aberrant expression acted as a diagnostic biomarker, indicating that SCD1 may play a role in tumorigenesis. We used ESCC as an example to demonstrate that SCD1 was dramatically upregulated in tumor tissues of ESCC and was associated with clinicopathological characteristics in ESCC patients. Furthermore, Kaplan-Meier analysis showed that high SCD1 expression was correlated with poor progression-free survival (PFS) and disease-free survival (DFS) in ESCC patients. The protein-protein interaction (PPI) network and module analysis by PINA database and Gephi were performed to identify the hub targets. Meanwhile, the functional annotation analysis of these hubs was constructed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Functionally, the gain-of-function of SCD1 in ESCC cells promoted cell proliferation, migration, and invasion; in contrast, loss-of-function of SCD1 in ESCC cells had opposite effects. Bioinformatic, QPCR, Western blotting and luciferase assays indicated that SCD1 was a direct target of miR-181a-5p in ESCC cells. In addition, gain-of-function of miR-181a-5p in ESCC cells reduced the cell growth, migratory, and invasive abilities. Conversely, inhibition of miR-181a-5p expression by its inhibitor in ESCC cells had opposite biological effects. Importantly, reinforced SCD1 in miR-181a-5p mimic ESCC transfectants reversed miR-181a-5p mimic-prevented malignant phenotypes of ESCC cells. Taken together, these results indicate that SCD1 expression influences tumor progression in a variety of cancers, and the miR-181a-5p/SCD1 axis may be a potential therapeutic target for ESCC treatment.

Keywords: ESCC; MiR-181a-5p; Stearoyl-CoA desaturase.