The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.
The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.
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lncRNA ZFAS1 通过结合聚腺苷酸结合蛋白 2 稳定 SREBP1 mRNA 来调节结直肠癌中的脂肪生成
DOI：
10.1016/j.omtn.2021.12.010
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Wang H;Chen Y;Liu Y;Li Q;Luo J;Wang L;Chen Y;Sang C;Zhang W;Ge X;Yao Z;Miao L;Liu X
结直肠癌（CRC）是全球癌症相关死亡的第四大原因。因此，需要更好地了解这种疾病的早期分子事件。长非编码RNA (lncRNA) 在肿瘤发生和癌症进展的调节中发挥着关键作用。在本研究中，我们研究了 ZFAS1 在 CRC 中的特性。我们分析了来自 GEO 的 CRC 组织的三个独立微阵列数据集，发现 ZFAS1 表达在所有三个数据集中均显着上调。此外，我们验证了ZFAS1在CRC组织中与正常组织相比的过度表达，发现ZFAS1与CRC的肿瘤大小和转移呈正相关。 ZFAS1 的敲低显着抑制了 CRC 细胞的恶性表型和脂肪生成。从机制上讲，ZFAS1结合聚腺苷酸结合蛋白2（PABP2）来稳定SREBP1 mRNA，从而增加SREBP1及其靶基因硬脂酰辅酶A去饱和酶（SCD1）和脂肪酸合酶（FASN）的表达，从而促进CRC脂质积累。这些数据表明，ZFAS1 可以作为 CRC 的癌基因，并且 ZFAS1 通过与 PABP2 结合来重新编程脂质代谢，以稳定 SREBP1 mRNA 的积累，这表明它是治疗 CRC 的新型有效靶标。结直肠癌（CRC）是全球癌症相关死亡的主要原因。刘等人。报道长非编码RNA ZFAS1调节脂肪酸合成，从而为CRC恶性表型转化提供生存优势，并且可能是CRC的潜在治疗靶点。
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. Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Liu et al. report that long noncoding RNA ZFAS1 regulates fatty acid synthesis, thereby providing survival advantages for malignant phenotype transformation of CRC, and may be a potential therapeutic target for CRC.
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DOI：
10.1002/hep.29654
发表时间：
2018-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Liu C;Yang Z;Wu J;Zhang L;Lee S;Shin DJ;Tran M;Wang L
通讯作者：
Wang L
影响因子：
50.3
作者：
Schild T;Low V;Blenis J;Gomes AP
通讯作者：
Gomes AP
影响因子：
5.8
作者：
Dong D;Mu Z;Zhao C;Sun M
通讯作者：
Sun M
DOI：
10.1261/rna.057026.116
发表时间：
2017-04
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Kühn U;Buschmann J;Wahle E
通讯作者：
Wahle E
影响因子：
9
作者：
Shan Y;Ma J;Pan Y;Hu J;Liu B;Jia L
通讯作者：
Jia L