Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer

Wei-Ching Chen; Chih-Yang Wang; Yu-Hsuan Hung; Tzu-Yang Weng; Meng-Chi Yen; Ming-Derg Lai

doi:10.1371/journal.pone.0155660

Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer

PLoS One. 2016 May 12;11(5):e0155660. doi: 10.1371/journal.pone.0155660. eCollection 2016.

Authors

Wei-Ching Chen¹, Chih-Yang Wang^{1

2}, Yu-Hsuan Hung^{1

2}, Tzu-Yang Weng¹, Meng-Chi Yen³, Ming-Derg Lai^{1

2

4}

Affiliations

¹ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
² Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
³ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
⁴ Center for Infectious Diseases and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.

Abstract

Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL) 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL family in individual type of cancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation
Coenzyme A Ligases / genetics*
Coenzyme A Ligases / metabolism
Gene Expression Regulation, Enzymologic*
Gene Expression Regulation, Neoplastic*
Humans
Neoplasms / enzymology*
Neoplasms / genetics*
Neoplasms / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Treatment Outcome

Substances

RNA, Messenger
RNA, Small Interfering
Coenzyme A Ligases
long-chain-fatty-acid-CoA ligase

Grants and funding

This study is supported by the grant from Ministry of Science and Technology (MOST 104-2325-B-006-004), Taiwan to MD Lai. This work was also supported by grant NHRI-EX100-9927B1 from the National Health Research Institute, Taiwan.