Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis
Abnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Transmission electron microscopy and nanoparticle tracking analysis were conducted to...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2025.2510041 |
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| author | Yiqian Liu Ling Zhang Jian Wang Jiali Xu Jing Xu Mengyan Xie Rong Wang |
| author_facet | Yiqian Liu Ling Zhang Jian Wang Jiali Xu Jing Xu Mengyan Xie Rong Wang |
| author_sort | Yiqian Liu |
| collection | DOAJ |
| description | Abnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Transmission electron microscopy and nanoparticle tracking analysis were conducted to verify NSCLC cell-derived small extracellular vesicles (sEVs). MicroRNA (miRNA/miR) and mRNA expression levels were determined using reverse transcription-quantitative PCR, while protein expression levels were determined using western blot analysis and immunofluorescence. In addition, potential binding sites between miR-326 and SNHG12/SLC7A11 were verified using a dual-luciferase reporter assay. Cell behavior was detected using flow cytometry, colony formation, wound healing and Transwell assays, and xenograft experiments were conducted to confirm the roles of SNHG12 in NSCLC. H&E staining was used for histological analysis, and each experiment was repeated three times. Results of the present study demonstrated that NSCLC-derived SNHG12 promoted type-2 tumor-associated macrophage (TAM2) polarization. However, the decrease of SNHG12 expression in EVs reduced TAM2 polarization, weakened NSCLC cell proliferation, migration and invasion, and promoted tumor cell ferroptosis. Moreover, results of the present study revealed that SNHG12 knockdown markedly suppressed tumor growth and the metastasis of NSCLC. In addition, SNHG12 upregulated SLC7A11 expression via binding to miR-326. Overexpressed SLC7A11 promoted tumor aggressiveness and suppressed the ferroptosis of NSCLC cells. Collectively, results of the present study revealed that SNHG12 suppressed ferroptosis and promoted the metastasis of NSCLC, further demonstrating that high SNHG12 expression levels may be indicative of poor clinical outcomes for patients with NSCLC. Thus, the present study highlighted that the SNHG12/miR-326/SLC7A11 axis may exhibit potential as a novel target for the treatment of NSCLC. |
| format | Article |
| id | doaj-art-83878abde3f4453a9a89eecef469e003 |
| institution | OA Journals |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-83878abde3f4453a9a89eecef469e0032025-08-20T02:29:41ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2510041Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axisYiqian Liu0Ling Zhang1Jian Wang2Jiali Xu3Jing Xu4Mengyan Xie5Rong Wang6Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Jintan Hospital Affiliated to Jiangsu University, Changzhou, ChinaDepartment of Oncology, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaAbnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Transmission electron microscopy and nanoparticle tracking analysis were conducted to verify NSCLC cell-derived small extracellular vesicles (sEVs). MicroRNA (miRNA/miR) and mRNA expression levels were determined using reverse transcription-quantitative PCR, while protein expression levels were determined using western blot analysis and immunofluorescence. In addition, potential binding sites between miR-326 and SNHG12/SLC7A11 were verified using a dual-luciferase reporter assay. Cell behavior was detected using flow cytometry, colony formation, wound healing and Transwell assays, and xenograft experiments were conducted to confirm the roles of SNHG12 in NSCLC. H&E staining was used for histological analysis, and each experiment was repeated three times. Results of the present study demonstrated that NSCLC-derived SNHG12 promoted type-2 tumor-associated macrophage (TAM2) polarization. However, the decrease of SNHG12 expression in EVs reduced TAM2 polarization, weakened NSCLC cell proliferation, migration and invasion, and promoted tumor cell ferroptosis. Moreover, results of the present study revealed that SNHG12 knockdown markedly suppressed tumor growth and the metastasis of NSCLC. In addition, SNHG12 upregulated SLC7A11 expression via binding to miR-326. Overexpressed SLC7A11 promoted tumor aggressiveness and suppressed the ferroptosis of NSCLC cells. Collectively, results of the present study revealed that SNHG12 suppressed ferroptosis and promoted the metastasis of NSCLC, further demonstrating that high SNHG12 expression levels may be indicative of poor clinical outcomes for patients with NSCLC. Thus, the present study highlighted that the SNHG12/miR-326/SLC7A11 axis may exhibit potential as a novel target for the treatment of NSCLC.https://www.tandfonline.com/doi/10.1080/15384047.2025.2510041Non-small cell lung cancersEVsSNHG12metastasisferroptosis |
| spellingShingle | Yiqian Liu Ling Zhang Jian Wang Jiali Xu Jing Xu Mengyan Xie Rong Wang Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis Cancer Biology & Therapy Non-small cell lung cancer sEVs SNHG12 metastasis ferroptosis |
| title | Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis |
| title_full | Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis |
| title_fullStr | Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis |
| title_full_unstemmed | Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis |
| title_short | Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis |
| title_sort | lung cancer cell derived sevs enhance the metastasis of non small cell lung cancer via snhg12 mir 326 slc7a11 axis |
| topic | Non-small cell lung cancer sEVs SNHG12 metastasis ferroptosis |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2025.2510041 |
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