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miR-93-5p 的作用及其在非小细胞肺癌中的放射抵抗拮抗效应。

Role of miR-93-5p and Its Opposing Effect of Ionizing Radiation in Non-Small Cell Lung Cancer.

机构信息

Department of Oncology Jiangsu Taizhou People's Hospital, The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou School of Clinical Medicine Nanjing Medical University, Taizhou 225300, China.

Department of General Surgery Jiangsu Taizhou People's Hospital, The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou School of Clinical Medicine Nanjing Medical University, Taizhou 225300, China.

出版信息

Anal Cell Pathol (Amst). 2024 Aug 10;2024:4218464. doi: 10.1155/2024/4218464. eCollection 2024.

Abstract

BACKGROUND

Radiation therapy is an effective local therapy for lung cancer. However, the interaction between genes and radiotherapy is multifaceted and intricate. Therefore, we explored the role of miR-93-5p in the proliferation, apoptosis, and migration abilities of A549 cells. Simultaneously, we also investigated the interactions between miR-93-5p and ionizing radiation (IR).

METHODS

Cell Counting Kit-8, transwell, and apoptotic assay were performed to measure the proliferation, migration, and apoptosis abilities. The expression levels of miR-93-5p and its target gene in lung cancer were predicted using starBase v3.0. Then, data were validated using qPCR and western blot.

RESULTS

miR-93-5p significantly promoted the proliferation ( < 0.01) and migration abilities ( < 0.001) of A549 cells. Gasdermin E (GSDME) was identified to be a putative target of miR-93-5p and had a negative correlation with miR-93-5p ( < 0.001). Overexpression of miR-93-5p significantly decreased GSDME in A549 ( < 0.001). Interestingly, miR-93-5p decreased cell proliferation ( < 0.01) and cell migration ( < 0.01) and increased apoptosis ( < 0.01) in A549 cells after exposure to IR.

CONCLUSIONS

miR-93-5p is presumed to play an oncogenic role in lung cancer by enhancing A549 cell proliferation and migration. It can enhance the sensitivity of radiotherapy under IR conditions. We speculate that the miR-93-5p/GSDME pathway was inhibited, activating the GSDME-related pyroptosis pathway when the cells were exposed to IR. Therefore, miR-93-5p can overcome resistance to radiotherapy and improve the efficacy of radiotherapy.

摘要

背景

放射治疗是肺癌的一种有效局部治疗方法。然而,基因与放射治疗之间的相互作用是多方面和复杂的。因此,我们探讨了 miR-93-5p 在 A549 细胞增殖、凋亡和迁移能力中的作用。同时,我们还研究了 miR-93-5p 与电离辐射(IR)之间的相互作用。

方法

使用细胞计数试剂盒-8、transwell 和凋亡测定法来测量增殖、迁移和凋亡能力。使用 starBase v3.0 预测肺癌中 miR-93-5p 和其靶基因的表达水平。然后,使用 qPCR 和 Western blot 验证数据。

结果

miR-93-5p 显著促进 A549 细胞的增殖( < 0.01)和迁移能力( < 0.001)。Gasdermin E(GSDME)被鉴定为 miR-93-5p 的一个假定靶基因,与 miR-93-5p 呈负相关( < 0.001)。miR-93-5p 的过表达显著降低了 A549 中的 GSDME( < 0.001)。有趣的是,miR-93-5p 在 A549 细胞暴露于 IR 后,降低了细胞增殖( < 0.01)和细胞迁移( < 0.01),并增加了细胞凋亡( < 0.01)。

结论

miR-93-5p 通过增强 A549 细胞的增殖和迁移,被认为在肺癌中发挥致癌作用。它可以增强 IR 条件下放射治疗的敏感性。我们推测,当细胞暴露于 IR 时,miR-93-5p/GSDME 通路被抑制,激活了与 GSDME 相关的细胞焦亡通路。因此,miR-93-5p 可以克服放疗抵抗,提高放疗疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c621/11330335/ca01ec776096/ACP2024-4218464.001.jpg

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