Restoring the epigenetically silenced lncRNA COL18A1-AS1 represses ccRCC progression by lipid browning via miR-1286/KLF12 axis

Yuenan Liu; Jun Wang; Yi Shou; Wenjie Xu; Ziwei Huang; Jiaju Xu; Kailei Chen; Jingchong Liu; Di Liu; Huageng Liang; Hongmei Yang; Xiaoping Zhang

doi:10.1038/s41419-022-04996-2

Cell Death and Disease (Jul 2022)

Restoring the epigenetically silenced lncRNA COL18A1-AS1 represses ccRCC progression by lipid browning via miR-1286/KLF12 axis

Yuenan Liu,
Jun Wang,
Yi Shou,
Wenjie Xu,
Ziwei Huang,
Jiaju Xu,
Kailei Chen,
Jingchong Liu,
Di Liu,
Huageng Liang,
Hongmei Yang,
Xiaoping Zhang

Affiliations

Yuenan Liu: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jun Wang: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yi Shou: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wenjie Xu: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Ziwei Huang: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jiaju Xu: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Kailei Chen: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jingchong Liu: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Di Liu: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Huageng Liang: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Hongmei Yang: Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology
Xiaoping Zhang: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

DOI: https://doi.org/10.1038/s41419-022-04996-2
Journal volume & issue: Vol. 13, no. 7
pp. 1 – 14

Abstract

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Abstract Abnormal accumulation of lipids has been highlighted in the progression of clear cell renal cell carcinoma (ccRCC). However, the underlying mechanism remains unclear. Emerging evidence suggests long noncoding RNAs (lncRNAs) participate in the regulation of lipid metabolism. In this study, we found lncRNA COL18A1-AS1 was downregulated in ccRCC and that higher COL18A1-AS1 expression indicated better prognosis. Decreased COL18A1-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. Restoring the epigenetically silenced COL18A1-AS1 repressed tumor progression, promoted lipid browning and consumption in vitro and in vivo. Mechanistically, COL18A1-AS1 could competitively bind miR-1286 to increase the expression of Krüppel-like factor 12 (KLF12). Downregulation of COL18A1-AS1 in ccRCC resulted in the low expression of KLF12. COL18A1-AS1/KLF12 positively regulated uncoupling protein 1 (UCP1)–mediated lipid browning, which promotes tumor cell “slimming” and inhibits tumor progression. When tumor cell “slimming” occurred, lipid droplets turned into tiny pieces, and lipids were consumed without producing ATP energy. Taken together, our findings on COL18A1-AS1-miR-1286/KLF12 axis revealed a potential mechanism of abnormal accumulation of lipids in ccRCC and could be a promising therapeutic target for ccRCC patients.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

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