ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting

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.