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  • Title: MicroRNA expression profiling and the role of ALCAM modulating tumor growth and metastasis in benzo[a]pyrene-transformed 16HBE cells.
    Author: Li L, Chen J, Wang Y, Zhou C, Ma X, Fu J, Yao B, Zhao P.
    Journal: Toxicology; 2020 Sep; 442():152539. PubMed ID: 32681969.
    Abstract:
    Benzo[a]pyrene (BaP) is a potent carcinogen and microRNAs (miRNAs) may play an important role in carcinogenesis. Activated leukocyte cell adhesion molecule (ALCAM) was up-regulated in BaP-transformed 16HBE cell line (THBEc1), and may be a key molecule for THBEc1 cells to gain and maintain the malignant phenotype. Here we screened the differentially expressed miRNAs which resulted in up-regulation of ALCAM in THBEc1 cells by comparing miRNA expression profiles between THBEc1 and 16HBE (HBE) cells. Results showed that a total of 555 miRNAs differentially expressed between THBEc1 and HBE cells, of which 351 miRNAs were down-regulated and 204 miRNAs were up-regulated in THBEc1 cells. MiR-152-3p, miR-142-5p and miR-211-5p down-regulated in THBEc1 cells were demonstrated to participate in the regulation of ALCAM. With THBEc1 as a tumor cell model, we determined the role of ALCAM in tumor growth and metastasis employing two ALCAM knockout THBEc1 cell lines via CRISPR/Cas9 technology. Results showed that ALCAM knockout inhibited colony formation and tumor growth, but enhanced cell migration and lung metastasis of THBEc1 cells. In conclusion, miR-152-3p/ALCAM, miR-142-5p/ALCAM and miR-211-5p/ALCAM axes may be involved in BaP-induced carcinogenesis. BaP might induce up-regulation of ALCAM via inhibiting miR-152-3p, miR-142-5p and miR-211-5p, which in turn allows ALCAM to exert its role promoting cell proliferation and tumor growth, and suppressing cell migration and metastasis.
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