Downregulation of miR‑429 and inhibition of cell migration and invasion in nasopharyngeal carcinoma

miR-429下调对鼻咽癌细胞迁移和侵袭的抑制

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作者:Fangzheng Wang, Chuner Jiang, Quanquan Sun, Fenqin Yan, Lei Wang, Zhenfu Fu, Tongxin Liu, Fujun Hu

Abstract

Viral, dietary and genetic factors have been implicated in nasopharyngeal carcinoma (NPC), however, the molecular mechanism underlying its pathogenesis remains to be fully elucidated. MicroRNAs (miRNAs) have been reported to be important in NPC tumorigenesis, with a previous miRNA microarray study showing the downregulation of miRNA (miR)‑429 in NPC cells. However, the possible mechanisms of action of miR‑429 have not been examined. In the present study, the expression profiles of miR‑429 were detected using reverse transcription‑quantitative polymerase chain reaction analysis in CNE‑1 and CNE‑2 cells, which are two generally used NPC cells with different degrees of differentiation. Subsequently, cell proliferation, invasion and migration were analyzed in miR‑429‑overexpressing CNE‑2 cells, and the modulatory function of miR‑429 was also investigated using two target genes, zinc finger E‑Box‑binding homeobox 1 (ZEB1) and CRK‑like (CRKL), by transfection with miR‑429 mimic or anti‑miR‑429. Significant changes in the expression of miR‑429 were detected, particularly in low‑differentiated CNE‑2 cells, with higher levels of epidemicity and malignancy. Additional results revealed that miR‑429 inhibited the invasion and migration of the CNE‑2 cells, whereas no significant effect on cell growth was observed. In addition, the mRNA and protein expression levels of the two target genes, ZEB1 and CRKL, were negatively regulated by miR‑429, demonstrated through gain‑of‑function and loss‑of‑function investigations, indicating that these two functional downstream targets may be involved in the inhibitory effects of miR‑429 on NPC migration and invasion. miR‑429 may act as a negative regulatory factor of NPC tumorigenesis, involving the functions of its downstream targets, ZEB1 and CRKL. The results suggested miR‑429 as a potential candidate for miRNA‑based prognosis or therapy against NPC.

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