Nickel (Ni) compounds are well-recognized human carcinogens, yet the molecular mechanisms by which they cause human cancer are still not well understood. MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in diverse biological functions and carcinogenesis. In previous study, we identified upregulation of DNA methyltransferase 1 (DNMT1) expression in nickel sulfide (NiS)-transformed human bronchial epithelial (16HBE) cells. Here, we investigated whether some miRNAs are aberrantly expressed and targets DNMT1 in NiS-transformed cells. Our results showed that the expression of miRNA-152 (miR-152) was specifically downregulated in NiS-transformed cells via promoter DNA hypermethylation, whereas ectopic expression of miR-152 in NiS-transformed cells resulted in a marked reduction of DNMT1 expression. Further experiments revealed that miR-152 directly downregulated DNMT1 expression by targeting the 3' untranslated regions of its transcript. Interestingly, treatment of DNMT inhibitor, 5-aza-2-deoxycytidine, or depletion of DNMT1 led to increased miR-152 expression by reversion of promoter hypermethylation, DNMT1 and MeCP2 binding to miR-152 promoter in NiS-transformed cells. Moreover, inhibition of miR-152 expression in 16HBE cells could increase DNMT1 expression and result in an increase in DNA methylation, DNMT1 and MeCP2 binding to miR-152 promoter, indicating an interaction between miR-152 and DNMT1 is regulated by a double-negative circuit. Furthermore, ectopic expression of miR-152 in NiS-transformed cells led to a significant decrease of cell growth. Conversely, inhibition of miR-152 expression in 16HBE cells significantly increased cell growth. Taken together, these observations demonstrate a crucial functional crosstalk between miR-152 and the DNMT1 via a feedback loop involved in NiS-induced malignant transformation.