Circ-SHPRH suppresses cadmium-induced transformation of human bronchial epithelial cells by regulating QKI expression via miR-224-5p

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the pathogenesis of human cancers and carcinogenesis of several environmental pollutants. Nevertheless, the function of circRNAs in cadmium carcinogenesis is unclear. circ-SHPRH is down-regulated in many cancers including non-small cell lung cancer. In our present study, during cadmium-induced transformation of human bronchial epithelial BEAS-2B cells, epithelial-mesenchymal transition (EMT) was induced. Meanwhile, at the middle and late stages of cell transformation, cadmium down-regulated the expression of circ-SHPRH, as well as QKI, a tumor suppressor protein known to prevent the proliferation and EMT during progression of human cancers, compared with passagematched control BEAS-2B cells. Overexpression of circ-SHPRH in cadmium-transformed BEAS-2B cells promoted the expression of QKI and significantly inhibited proliferation, EMT, invasion, migration and anchorageindependent growth in soft agar of the cells. Mechanistic studies showed that circ-SHPRH functioned as a sponge of miR-224-5p to regulate QKI expression. Interestingly, QKI and circ-SHPRH could form a positive-feedback loop that perpetuated circ-SHPRH/miR-224-5p/QKI axis. Collectively, our results demonstrated that circSHPRH inhibited cadmium-induced transformation of BEAS-2B cells through sponging miR-224-5p to regulate QKI expression under cadmium treatment. Our study uncovered a novel molecular mechanism involved in circRNAs in the development of lung cancer due to cadmium exposure.