RUNX2/miR‑31/SATB2 pathway in nickel‑induced BEAS‑2B cell transformation

Area of Science:

• Environmental Toxicology
• Molecular Carcinogenesis
• Cell Biology

Background:

• Nickel (Ni) compounds are Group 1 carcinogens, primarily targeting the lungs.
• Special AT-rich sequence-binding protein 2 (SATB2) was previously identified as crucial for Ni-induced BEAS-2B cell transformation.

Purpose of the Study:

• Investigate the regulatory pathway controlling SATB2 expression in Ni-transformed BEAS-2B cells.
• Elucidate the role of Runt-related transcription factor 2 (RUNX2) and miR-31 in nickel-induced carcinogenesis.

Main Methods:

• Western blotting and RT-qPCR to assess protein and gene expression.
• Soft agar, migration, and invasion assays to evaluate cell transformation and metastatic potential.

Main Results:

• RUNX2, a master regulator of osteogenesis and oncogene, was identified as an upstream regulator of SATB2.
• Ni exposure induced RUNX2 expression, promoting BEAS-2B cell transformation and metastasis.
• miR-31, a downstream target of RUNX2, was downregulated in Ni-transformed cells, maintaining cancer hallmarks.
• RUNX2 suppressed miR-31 expression, leading to increased SATB2 levels and subsequent cell transformation.
• Ni repressed miR-31 by modifying its promoter, thereby increasing SATB2 expression and driving cell transformation.

Conclusions:

• RUNX2-mediated suppression of miR-31 is a key mechanism in nickel-induced lung cell transformation.
• Targeting the RUNX2/miR-31/SATB2 axis may offer therapeutic strategies against nickel-induced lung cancer.