Abstract
Nickel (Ni) compounds are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) and are known to be carcinogenic to the lungs. In our previous study, special AT‑rich sequence‑binding protein 2 (SATB2) was required for Ni‑induced BEAS‑2B cell transformation. In the present study, a pathway that regulates the expression of SATB2 protein was investigated in Ni‑transformed BEAS‑2B cells using western blotting and RT‑qPCR for expression, and soft agar, migration and invasion assays for cell transformation. Runt‑related transcription factor 2 (RUNX2), a master regulator of osteogenesis and an oncogene, was identified as an upstream regulator for SATB2. Ni induced RUNX2 expression and initiated BEAS‑2B transformation and metastatic potential. Previously, miRNA‑31 was identified as a negative regulator of SATB2 during arsenic‑induced cell transformation, and in the present study it was identified as a downstream target of RUNX2 during carcinogenesis. miR‑31 expression was reduced in Ni‑transformed BEAS‑2B cells, which was required to maintain cancer hallmarks. The expression level of miR‑31 was suppressed by RUNX2 in BEAS‑2B cells, and this increased the expression level of SATB2, initiating cell transformation. Ni caused the repression of miR‑31 by placing repressive marks at its promoter, which in turn increased the expression level of SATB2, leading to cell transformation.