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ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting
Cell Biochemistry and Biophysics ( IF 2.6 ) Pub Date : 2021-03-16 , DOI: 10.1007/s12013-021-00976-z
Hong Deng 1 , Mingming Wang 1 , Qin Xu 1 , Hui Yao 1
Affiliation  

Colorectal cancer (CRC) belongs to one of gastric cancers that half of cases will develop metastasis, causing higher mortality or chemotherapy resistance. In the present study, the long noncoding RNA zinc finger antisense 1 (ZFAS1) was proved to have high expression level in CRC samples and in advanced stages. Additionally, it also indicated that p53 status is associated with ZFAS1 expression. Silencing ZFAS1 reduced both migration and invasion ability of DLD-1 and HCT-116 cells, which is relevant to the EMT process. In addition, it was confirmed that miR-34b, a tumor suppressor miRNA directly targeted ZFAS1 3′ untranslated region (3′UTR) and inhibited ZFAS1 expression. Furthermore, miR-34b partially reversed the effect of ZFAS1 on migration and invasion ability in DLD-1 cells. Meanwhile, p53 status changes by overexpression vectors or siRNA turbulent ZFAS1 expression. Besides, it was found that in most cases, the oncogene SOX4 was directly targeted by miR-34b and positive correlated to ZFAS1 expression. Silencing ZFAS1 induced SOX4 expression in DLD-1 cells. Our data demonstrated the functions and mechanisms of ZFAS1 in CRC metastasis, illustrating miR-34b directly targets ZFAS1 and inhibits metastasis ability of CRC cells. SOX4 is also the direct downstream target of miR-34b, and silencing ZFAS1 can inhibit SOX4 though modulating miR-34b.



中文翻译:

ZFAS1 通过调节 miR-34b/SOX4 靶向促进结直肠癌转移

大肠癌(CRC)属于胃癌之一,一半的病例会发生转移,导致更高的死亡率或化疗耐药。在本研究中,长链非编码 RNA 锌指反义 1 (ZFAS1) 被证明在 CRC 样本和晚期阶段具有高表达水平。此外,它还表明 p53 状态与 ZFAS1 表达相关。沉默 ZFAS1 降低了 DLD-1 和 HCT-116 细胞的迁移和侵袭能力,这与 EMT 过程有关。此外,证实miR-34b,一种肿瘤抑制miRNA,直接靶向ZFAS1 3'非翻译区(3'UTR)并抑制ZFAS1表达。此外,miR-34b 部分逆转了 ZFAS1 对 DLD-1 细胞迁移和侵袭能力的影响。同时,p53 状态因过表达载体或 siRNA 湍流 ZFAS1 表达而改变。此外,发现在大多数情况下,癌基因 SOX4 直接被 miR-34b 靶向,并且与 ZFAS1 表达呈正相关。沉默 ZFAS1 诱导 DLD-1 细胞中的 SOX4 表达。我们的数据证明了 ZFAS1 在 CRC 转移中的功能和机制,说明 miR-34b 直接靶向 ZFAS1 并抑制 CRC 细胞的转移能力。SOX4 也是 miR-34b 的直接下游靶标,沉默 ZFAS1 可以通过调节 miR-34b 抑制 SOX4。说明 miR-34b 直接靶向 ZFAS1 并抑制 CRC 细胞的转移能力。SOX4 也是 miR-34b 的直接下游靶标,沉默 ZFAS1 可以通过调节 miR-34b 抑制 SOX4。说明 miR-34b 直接靶向 ZFAS1 并抑制 CRC 细胞的转移能力。SOX4 也是 miR-34b 的直接下游靶标,沉默 ZFAS1 可以通过调节 miR-34b 抑制 SOX4。

更新日期:2021-03-16
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