Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway
Abstract Anesthesia and perioperative management significantly influence long-term outcomes in patients with early and intermediate stage cancer. Midazolam, a commonly used benzodiazepine anesthetic, has shown potential anti-tumor effects. This study aimed to explore the anti-tumor properties of mid...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-01625-8 |
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| author | Jinghua Jiao Yifang Tang Lu Ye Yaru Yang Zhenghua Liu |
| author_facet | Jinghua Jiao Yifang Tang Lu Ye Yaru Yang Zhenghua Liu |
| author_sort | Jinghua Jiao |
| collection | DOAJ |
| description | Abstract Anesthesia and perioperative management significantly influence long-term outcomes in patients with early and intermediate stage cancer. Midazolam, a commonly used benzodiazepine anesthetic, has shown potential anti-tumor effects. This study aimed to explore the anti-tumor properties of midazolam in non-small cell lung cancer (NSCLC). The anti-tumor effects of midazolam on A549 and H1650 NSCLC cell lines were assessed using CCK-8 assays, colony-forming assays, and the Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I. Additionally, Transwell assays were conducted in vitro, and subcutaneous tumor models in nude mice were established to assess the anti-tumor effects in vivo. The interaction within the lncRNA XLOC_010706/miR-520d-5p/STAT3 axis was confirmed through dual-luciferase reporter assays, RT-qPCR, and Western blotting. Midazolam significantly inhibited cell proliferation and invasion while inducing apoptosis in A549 and H1650 cells, both in vitro and in vivo, by promoting autophagy (P<0.05). It also down-regulated the expression of lncRNA XLOC_010706 in the tumor microenvironment (P<0.05). Within the signaling pathway, lncRNA XLOC_010706 functioned as a competing endogenous RNA (ceRNA) targeting miR-520d-5p, with STAT3 identified as a functional target gene for miR-520d-5p in NSCLC. Furthermore, lncRNA XLOC_010706 acted as an oncogene, promoting cell proliferation and invasion while inhibiting apoptosis through the miR-520d-5p/STAT3 axis. Midazolam down-regulates the expression of lncRNA XLOC_010706, which acts as an oncogene in NSCLC. The anti-tumor effects of midazolam occur via the lncRNA XLOC_010706/miR-520d-5p/STAT3 pathway, enhancing autophagy in NSCLC. This indicates that lncRNA XLOC_010706 could serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients. |
| format | Article |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d7255e89cd7c47de84ed32214db62d0c2025-08-20T03:10:14ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-01625-8Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathwayJinghua Jiao0Yifang Tang1Lu Ye2Yaru Yang3Zhenghua Liu4Department of Anesthesiology, Central Hospital Affiliated to Shenyang Medical CollegeDepartment of Anesthesiology, The Second Xiangya Hospital of Central South UniversityDepartment of Anesthesiology, Guangzhou Eighth People’s Hospital, Guangzhou Medical UniversityDepartment of Anesthesiology, Central Hospital Affiliated to Shenyang Medical CollegeDepartment of Thoracic Surgery, The First Affiliated Hospital of China Medical UniversityAbstract Anesthesia and perioperative management significantly influence long-term outcomes in patients with early and intermediate stage cancer. Midazolam, a commonly used benzodiazepine anesthetic, has shown potential anti-tumor effects. This study aimed to explore the anti-tumor properties of midazolam in non-small cell lung cancer (NSCLC). The anti-tumor effects of midazolam on A549 and H1650 NSCLC cell lines were assessed using CCK-8 assays, colony-forming assays, and the Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I. Additionally, Transwell assays were conducted in vitro, and subcutaneous tumor models in nude mice were established to assess the anti-tumor effects in vivo. The interaction within the lncRNA XLOC_010706/miR-520d-5p/STAT3 axis was confirmed through dual-luciferase reporter assays, RT-qPCR, and Western blotting. Midazolam significantly inhibited cell proliferation and invasion while inducing apoptosis in A549 and H1650 cells, both in vitro and in vivo, by promoting autophagy (P<0.05). It also down-regulated the expression of lncRNA XLOC_010706 in the tumor microenvironment (P<0.05). Within the signaling pathway, lncRNA XLOC_010706 functioned as a competing endogenous RNA (ceRNA) targeting miR-520d-5p, with STAT3 identified as a functional target gene for miR-520d-5p in NSCLC. Furthermore, lncRNA XLOC_010706 acted as an oncogene, promoting cell proliferation and invasion while inhibiting apoptosis through the miR-520d-5p/STAT3 axis. Midazolam down-regulates the expression of lncRNA XLOC_010706, which acts as an oncogene in NSCLC. The anti-tumor effects of midazolam occur via the lncRNA XLOC_010706/miR-520d-5p/STAT3 pathway, enhancing autophagy in NSCLC. This indicates that lncRNA XLOC_010706 could serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients.https://doi.org/10.1038/s41598-025-01625-8Non-small cell lung cancerMidazolamlncRNA XLOC_010706miR-520d-5pAutophagy |
| spellingShingle | Jinghua Jiao Yifang Tang Lu Ye Yaru Yang Zhenghua Liu Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway Scientific Reports Non-small cell lung cancer Midazolam lncRNA XLOC_010706 miR-520d-5p Autophagy |
| title | Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway |
| title_full | Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway |
| title_fullStr | Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway |
| title_full_unstemmed | Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway |
| title_short | Unraveling the anti-tumor effects of midazolam in non-small cell lung cancer through the lncRNA XLOC_010706/miR-520d-5p/STAT3/autophagy pathway |
| title_sort | unraveling the anti tumor effects of midazolam in non small cell lung cancer through the lncrna xloc 010706 mir 520d 5p stat3 autophagy pathway |
| topic | Non-small cell lung cancer Midazolam lncRNA XLOC_010706 miR-520d-5p Autophagy |
| url | https://doi.org/10.1038/s41598-025-01625-8 |
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