Hsa_circ_0004214 involved in the epithelial-mesenchymal transition induced by beryllium sulfate through modulating JAK-STAT signaling pathway.

BACKGROUND

Chronic beryllium disease is characterized by granulomas and pulmonary fibrosis. Recent studies have shown that microRNAs (miRNAs) and circular RNAs (circRNAs) play critical roles in the pathogenesis and development of many diseases. However, the role of miRNAs and circRNAs in pulmonary fibrosis induced by beryllium sulfate (BeSO) has not been elucidated.

METHODS

Previous studies demonstrated hsa-miR-663b was down-regulated in the 150 μmol/L BeSO-treated 16HBE cells, while hsa_circ_ 0004214 was up-regulated. Here we found epithelial-mesenchymal transition (EMT) involved in pulmonary fibrosis induced by BeSO (4, 8, and 12 mg/kg·BW) in SD rats.

RESULTS

Elevated expression of hsa-miR-663b blocked the EMT progression of 16HBE cells induced by 150 μmol/L BeSO. Notably, the overexpression of hsa-miR-663b decreased the expression of leukemia inhibitory factor (LIF), which was predicted as a target gene of hsa-miR-663b by bioinformatics tools. Furthermore, elevated miR-663b inhibited the activation of the downstream Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway induced by BeSO in 16HBE cells. Previous study suggested that hsa_circ_0004214 had binding sites for hsa-miR-663b. The results indicated hsa_circ_0004214 alleviated the BeSO-induced EMT via JAK-STAT pathway in 16HBE cells.

CONCLUSIONS

Collectively, the overexpression of hsa-miR-663b and knockdown of hsa_circ_0004214 attenuated the EMT induced by BeSO through the inhibition of JAK-STAT signaling pathway. The aberrant expressed hsa-miR-663b and hsa_circ_0004214 stimulated by BeSO may exert an important function in the toxic mechanism of beryllium exposure to 16HBE cells, providing the potential therapeutic targets in chronic beryllium disease.