In:
Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-8-23)
Abstract:
Polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene (B[a] P), found in cigarette smoke and air pollution, is an important carcinogen. Nevertheless, early molecular events and related regulatory effects of B[a]P-mediated cell transformation and tumor initiation remain unclear. This study found that EGR1 was significantly downregulated during human bronchial epithelial cell transformation and mice lung carcinogenesis upon exposure to B[a] P and its active form BPDE, respectively. In contrast, overexpression of EGR1 inhibited the BPDE-induced cell malignant transformation. Moreover, miR-377-3p was strongly enhanced by BPDE/B[a]P exposure and crucial for the inhibition of EGR1 expression by targeting the 3’UTR of EGR1. MiR-377-3p antagomir reversed the effect of EGR1 downregulation in cell malignant transformation and tumor initiation models. Furthermore, the B[a] P-induced molecular changes were evaluated by IHC in clinical lung cancer tissues and examined with a clinic database. Mechanistically, EGR1 inhibition was also involved in the regulation of Wnt/β-catenin transduction, promoting lung tumorigenesis following B[a]P/BPDE exposure. Taken together, the results demonstrated that bBenzo[a] pyrene exposure might induce lung tumorigenesis through miR-377-3p-mediated reduction of EGR1 expression, suggesting an important role of EGR1 in PAHs-induced lung carcinogenesis.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2021.699004
DOI:
10.3389/fonc.2021.699004.s001
DOI:
10.3389/fonc.2021.699004.s002
DOI:
10.3389/fonc.2021.699004.s003
DOI:
10.3389/fonc.2021.699004.s004
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2649216-7
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