Silencing of LINC01278 promotes sensitivity of non-small cell lung cancer cells to osimertinib by targeting miR-324-3p/ZFX axis

Osimertinib has been demonstrated to be effective for improving the prognosis of patients with epidermal growth factor receptor mutation-positive lung Cancer. However, osimertinib resistance inevitably emerges throughout the treatment course. This study explored the function and mechanism of long noncoding RNA LINC01278 in osimertinib-resistant NSCLC cells. Osimertinib-resistant non-small cell lung Cancer (NSCLC) cells were established by treating PC9 and HCC827 cells with increasing doses of osimertinib for over 6 months. LINC01278 expression in parental and drug-resistant cells (PC9-OR and HCC827-OR) was measured by polymerase chain reaction. Cell counting kit 8 assays were used to examine cell viability and half-maximal inhibitory concentration values. The effects of LINC01278 knockdown on cell proliferation and Apoptosis were measured by colony formation assays and flow cytometry. A luciferase reporter assay was performed to verify the interaction between LINC01278 and miR-324-3p or the binding ability between miR-324-3p and ZFX. Protein levels of ZFX and apoptotic markers in NSCLC cells were measured by western blotting. As shown by experimental results, LINC01278 was highly expressed in osimertinib-resistant NSCLC cells compared to its expression in parental cells. The silencing of LINC01278 improved the sensitivity of drug-resistant cells towards osimertinib. LINC1278 depletion inhibited osimertinib-resistant cell proliferation while promoting cell Apoptosis. LINC01278 interacted with miR-324-3p to regulate ZFX expression. ZFX could be targeted by miR-324-3p in PC9-OR and HCC827-OR cells. ZFX overexpression counteracted the suppressive impact of LINC01278 silencing on the malignant behavior of PC9-OR and HCC827-OR cells. In conclusion, LINC01278 knockdown alleviates osimertinib resistance of NSCLC cells by regulating downstream miR-324-3p and ZFX.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00673-8.

LINC01278; NSCLC; Osimertinib; Zinc finger protein X-linked; miR-324-3p.