The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA

Huishan Wang; Yuli Chen; Yanwen Liu; Qiuhui Li; Jing Luo; Li Wang; Yuanyuan Chen; Chen Sang; Wen Zhang; Xianxiu Ge; Zhifeng Yao; Lin Miao; Xianghua Liu

Molecular Therapy: Nucleic Acids (Mar 2022)

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA

Huishan Wang,
Yuli Chen,
Yanwen Liu,
Qiuhui Li,
Jing Luo,
Li Wang,
Yuanyuan Chen,
Chen Sang,
Wen Zhang,
Xianxiu Ge,
Zhifeng Yao,
Lin Miao,
Xianghua Liu

Affiliations

Huishan Wang: Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai 210000, China
Yuli Chen: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
Yanwen Liu: Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210000, China; Corresponding author: Yanwen Liu, Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210000, China.
Qiuhui Li: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
Jing Luo: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210011, China
Li Wang: Department of Oncology, The Third Medical School of Nanjing Medical University, Nanjing 210011, China
Yuanyuan Chen: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
Chen Sang: Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow of University, Changzhou G 213003, China
Wen Zhang: Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210000, China
Xianxiu Ge: Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai 210000, China
Zhifeng Yao: Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow of University, Changzhou G 213003, China
Lin Miao: Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Corresponding author: Lin Miao, Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Xianghua Liu: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China; Corresponding author: Xianghua Liu, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.

Journal volume & issue: Vol. 27
pp. 363 – 374

Abstract

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Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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