Quan Lei, Ping Liu, Xinlei Guan, Li Liu, Wenjuan He
{"title":"沉默LINC01278通过靶向miR-324-3p/ZFX轴促进非小细胞肺癌细胞对奥西替尼的敏感性。","authors":"Quan Lei, Ping Liu, Xinlei Guan, Li Liu, Wenjuan He","doi":"10.1007/s10616-024-00673-8","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00673-8.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"23"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659544/pdf/","citationCount":"0","resultStr":"{\"title\":\"Silencing of LINC01278 promotes sensitivity of non-small cell lung cancer cells to osimertinib by targeting miR-324-3p/ZFX axis.\",\"authors\":\"Quan Lei, Ping Liu, Xinlei Guan, Li Liu, Wenjuan He\",\"doi\":\"10.1007/s10616-024-00673-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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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.
期刊介绍：
The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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