The miR-221/222 regulates the ID1 gene expression through PTEN, c-JUN and ARF4 mediators to control cell proliferation

Abstract

Objective: To explore the effect of miR-221/222 on cell proliferation and regulation of inhibitor of differentiation1 (ID1) expression concerning the value of miR-221/22 in cancer diagnosis, prognosis, or therapeutic use. Methods: Embryonic cell line (HEK293), breast cancer cell line (MCF7), and lymphoblast cell line (U937) were employed to investigate cell proliferation in the presence or absence of miR-221/222 using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The relation of miR-221/222 and expression of the ID1 gene was monitored via luciferase activity and real-time PCR. Quantitative PCR was used to detect the effect of miR-221/222 on the expression of cellular proteins, c-JUN, ARF4, and PTEN. Results: The miR-221/222 significantly increased the expression level of the ID1 gene in MCF7 and U937 cell lines but downregulation of the ID1 gene was revealed for transfected HEK293 cells. Level of the ID1 mRNA showed that miR-221/222 regulated the ID1 gene expression at the transcriptional level. Moreover, miR-221/222 enhanced the cellular proteins, ARF4 and c-JUN, and expression in MCF7 and U937, while inhibiting them in HEK293. These findings indicated that the effect of miR-221/222 on ARF4 and c-JUN expression in HEK293 may be mediated by different pathways from MCF7 and U937. Conclusions: Increasing levels of miR-221/222 expression are correlated with cell proliferation and the regulation of ID1 expression. ID1 regulation is a complex process and miR-221/222 may regulate its expression via c-JUN and ARF4. The value of miR-221/22 in cancer diagnosis, prognosis, or therapeutic use may be cancer type dependent.