A Novel Regulatory Network of Noncoding RNAs in the Cadmium-Induced Malignant Transformation of Human Bronchial Epithelial Cells.

Abstract

Long-term exposure to cadmium (Cd) is closely linked to an increased risk of lung cancer, yet the underlying mechanisms driving this malignant transformation remain elusive. Noncoding RNAs may hold the key to understanding the complex pathways involved in cadmium-induced carcinogenesis. This study reveals a novel regulatory network involving circ_000877, lnc237177, and miR-3192-5p, which targets cyclin-D1(CCND1) and matrix metalloproteinase 2 (MMP-2), thereby promoting the Cd-induced malignant transformation of human bronchial epithelial (16HBE) cells. Utilizing an established 16HBE malignant transformation model induced by Cd exposure, RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that both circ_000877 and lnc237177 were significantly upregulated. Functional assays further confirmed the roles of these molecules in facilitating malignant transformation. Mechanistically, circ_000877 and lnc237177 collaboratively targeted miR-3192-5p, thereby modulating both mRNA and protein expression levels of cyclin-D1 and MMP-2. Collectively, this study offers novel perspectives into the mechanism through which circRNA and lncRNA jointly regulate miRNA in a crosstalk network during Cd-induced malignant transformation, thereby enhancing our understanding of cadmium's toxicological impact.