We identified circ-TMX4 as a downstream target of ERβ that affects NSCLC invasion by acting as a miR-622 sponge and regulating CXCR4 expression, thereby a novel mechanism by which ERβ modulates circ-TMX4/miR-622 signaling to impact NSCLC cell invasion. The gene discussed is TMX4; the disease is non-small cell lung carcinoma.