Abstract
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.
Highlights
Colorectal cancer (CRC) is the fourth most common malignant tumor in the world, with almost 900,000 deaths annually, and is mainly caused by distant metastasis.[1]
ZNFX1 antisense RNA1 (ZFAS1) is overexpressed in CRC and associated with poor prognosis To screen for aberrantly expressed Long noncoding RNAs (lncRNAs) in CRC, we downloaded three CRC tissue microarray datasets (GSE5206, GSE21510, and GSE9348) from the Gene Expression Omnibus (GEO) and analyzed the differentially expressed lncRNAs
Further analysis of The Cancer Genome Atlas (TCGA) data revealed that ZFAS1 was upregulated in CRC among the six digestive system tumors esophageal carcinoma (ESCA), esophageal carcinoma (STAD), colon adenocarcinoma (COAD), cholangio carcinoma (CHOL), pancreatic adenocarcinoma (PAAD), and liver hepatocellular carcinoma (LIHC) (Figure 1B)
Summary
Colorectal cancer (CRC) is the fourth most common malignant tumor in the world, with almost 900,000 deaths annually, and is mainly caused by distant metastasis.[1]. Aerobic glycolysis and increased glutamine metabolism are crucial for cancer cells to be shed from a primary tumor, to overcome nutrient and energy deficits, and eventually survive and form metastases.[4,5] a better understanding of the early metabolic events associated with the CRC malignant phenotype is warranted to decrease mortality and prolong patient survival
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