Elevated SNHG1 promotes invasion and migration of Cd(II)-transformed cells through Sox2, Rac1, and Slug

Abstract

Numerous studies have shown that exposure to cadmium [Cd(II)] contributes to the development of cancers in the lung and other organs. Cd(II) compounds are classified as confirmed human carcinogens; however, the mechanisms underlying Cd(II)-induced carcinogenesis remain poorly understood. Small nucleolar RNA host gene 1 (SNHG1), a long non-coding RNA (lncRNA), has been identified as an oncogene. In this study, we investigated the role of SNHG1 in the invasion and migration of Cd(II)-transformed cells. Our findings revealed that SNHG1 expression was significantly elevated in Cd(II)-transformed cells compared to their passage-matched normal BEAS-2B counterparts. Silencing SNHG1 reduced the invasive and migratory capacities of Cd(II)-transformed cells and inhibited malignant transformation induced by long-term Cd exposure. Notably, ectopic expression of SNHG1 alone in BEAS-2B cells was sufficient to drive malignant transformation and enhance invasion and migration, underscoring its oncogenic potential. SRY-box 2 (Sox2), a transcription factor implicated in cancer cell proliferation, invasion, and migration, was found to be upregulated in Cd(II)-transformed cells, while SNHG1 knockdown led to decreased Sox2 protein levels. Similarly, ras-related C3 botulinum toxin substrate 1 (Rac1), a key regulator of cytoskeletal dynamics linked to tumor growth, invasion, and metastasis, was also elevated in Cd(II)-transformed cells. Knockdown of SNHG1 reduced Rac1 protein levels, and Rac1 knockout significantly suppressed invasion and migration. Additionally, we observed increased expression of Slug, a key transcription factor invovlved in epithelial-mesenchymal transition (EMT), and decreased expression of its downstream target E-cadherin in Cd(II)-transformed cells. Collectively, these results demonstrate that elevated SNHG1 promotes the expression of Sox2, Rac1, and Slug, thereby driving the invasive and migratory behavior of Cd(II)-transformed cells.