Arteannuin B Inhibits NSCLC Cells via Regulating miR-194-3p/CLDN2 Axis

Arteannuin B (Art B), a sesquiterpene lactone from Artemisia annua, combats non-small cell lung cancer (NSCLC) chemoresistance by activating a novel miR-194-3p/CLDN2 axis, as identified here through integrated transcriptomic and functional analyses. Here, we combined transcriptomic profiling with functional validation to identify claudin-2 (CLDN2) as a critical mediator of Art B's anticancer effects in NSCLC. CLDN2, significantly upregulated in NSCLC tissues versus paired normal tissues, promoted tumor cell proliferation and cisplatin resistance by upregulating multidrug resistance-associated protein 2 (MRP2). Mechanistically, miR-194-3p directly binds to two conserved sites (nt 358-365 and 1232-1238) within the CLDN2 3' UTR, suppressing its expression via mRNA degradation and translational inhibition, thereby attenuating proliferation and resensitizing cells to cisplatin. Importantly, Art B exerted antitumor effects by upregulating miR-194-3p, which subsequently inhibited CLDN2. This study not only elucidates a previously unrecognized mechanism for overcoming chemoresistance but also nominates CLDN2 as a prognostic biomarker, offering a promising therapeutic strategy that could benefit NSCLC patients facing treatment failure.