National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune 411007, India.
Oncotarget. 2022 May 24;13:725-746. doi: 10.18632/oncotarget.28233. eCollection 2022.
Non-small cell lung cancer (NSCLC) is considered to have more than 80% of all lung cancer cases, making it the leading cause of cancer-related deaths globally. MicroRNA (miRNA) deregulation has been seen often in NSCLC and has been linked to the disease's genesis, progression, and metastasis via affecting their target genes.
Our study focused on the functionality of down-regulated miRNAs in NSCLC. For this study, we used 91 miRNAs reported to be down-regulated in NSCLC. The targets of these miRNAs were chosen from miRNA databases with functionality in NSCLC, including miRBase, miRDB, miRTV, and others. Inter-regulatory miRNA-NSCLC networks were generated. Simulated annealing was used to improve the network's resilience and understandability. GSEA was used to examine 24607 genes reported experimentally in order to gain physiologically relevant information about the target miR-520c-3p.
The study revealed functional prominence on miR-520c-3p, down-regulated during NSCLC. The involvement of miR-520c-3p in the PI3K/AKT/mTOR signaling pathway was recognized.
The therapeutic usage by designing a synthetic circuit of miR-520c-3p was explored, which may help in suppressing tumors in NSCLC. Our study holds promise for the successful deployment of currently proposed miRNA-based therapies for malignant disorders, which are still in the early pre-clinical stages of development.
非小细胞肺癌(NSCLC)被认为占所有肺癌病例的 80%以上,是全球癌症相关死亡的主要原因。miRNA(miRNA)失调在 NSCLC 中经常出现,并通过影响其靶基因与疾病的发生、进展和转移有关。
我们的研究侧重于 NSCLC 中下调 miRNA 的功能。在这项研究中,我们使用了 91 种报道在 NSCLC 中下调的 miRNA。这些 miRNA 的靶基因是从 miRNA 数据库中选择的,这些数据库在 NSCLC 中具有功能,包括 miRBase、miRDB、miRTV 等。生成了相互调节的 miRNA-NSCLC 网络。模拟退火用于提高网络的弹性和可理解性。GSEA 用于检查 24607 个在实验中报道的基因,以获得关于靶 miR-520c-3p 的生理相关信息。
研究揭示了 miR-520c-3p 在 NSCLC 下调期间的功能重要性。识别了 miR-520c-3p 参与 PI3K/AKT/mTOR 信号通路。
通过设计 miR-520c-3p 的合成电路来探索治疗用途,这可能有助于抑制 NSCLC 中的肿瘤。我们的研究为成功部署目前提出的针对恶性疾病的 miRNA 治疗方法提供了希望,这些方法仍处于早期临床前开发阶段。