Fine particulate matter (PM_2.5) induces the stem cell-like properties of hepatocellular carcinoma by activating...

Exposure to fine particulate matter (PM_2.5) has been linked to an increased incidence and mortality of hepatocellular carcinoma (HCC). However, the impact of PM_2.5 exposure on HCC progression and the underlying mechanisms remain largely unknown. This study aimed to investigate the effects of PM_2.5 exposure on the stem cell-like properties of HCC cells. Our findings indicate that PM_2.5 exposure significantly enhances the stemness of HCC cells (p < 0.01). Subsequently, male nude mice were divided into two groups (n = 8/group for tumor-bearing assay, n = 5/group for metastasis assay) for control and PM_2.5 exposure. In vivo assays revealed that exposure to PM_2.5 promoted the growth, metastasis, and epithelial-mesenchymal transition (EMT) of HCC cells (p < 0.01). Further exploration demonstrated that PM_2.5 enhances the stemness of HCC cells by inducing cellular reactive oxygen species (ROS) generation (p < 0.05). Mechanistic investigation indicated that elevated intracellular ROS inhibited kelch-like ECH-associated protein 1 (Keap1) levels, promoting the upregulation and nucleus translocation of NFE2-like bZIP transcription factor 2 (Nrf2). This, in turn, induced autophagy activation, thereby promoting the stemness of HCC cells (p < 0.01). Our present study demonstrates the adverse effects of PM_2.5 exposure on HCC development and highlights the mechanism of ROS/Nrf2/Keap1-mediated autophagy. For the first time, we reveal the impact of PM_2.5 exposure on the poor prognosis-associated cellular phenotype of HCC and its underlying mechanism, which is expected to provide new theoretical basis for the improvement of public health.