Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.

肺癌仍然是全世界癌症相关死亡的主要原因。由于 microRNA (miRNA) 与肺癌密切相关，我们通过 ALX4/NCAM1/MAPK 轴研究了 miR-324-3p 在肺癌中的潜在作用。在临床样本中检测到 miR-324-3p 和 ALX4 的表达，并通过 miRNA 靶向荧光素酶报告基因测定证实了它们的相互作用。通过获得和损失功能方法分析了肺癌细胞生物学过程中 miR-324-3p-ALX4 相互作用的机制。此外，培养的肺癌细胞用 p38MAPK 通路激活剂 P79350 处理，以探索该通路在上述轴中的作用。此外，构建了裸鼠肿瘤异种移植模型以证实体外研究结果。miR-324-3p在肺癌组织和细胞中高表达，抑制A549细胞中ALX4的表达。在确认 miR-324-3p 对 ALX4 的靶向抑制后，我们发现这种相互作用上调了 NCAM1 的表达并激活了 MAPK 通路。抑制miR-324-3p可以抑制肺癌细胞的侵袭、迁移和自噬，延缓裸鼠皮下肿瘤的生长。ALX4 或 NCAM1 过表达的下调逆转了 miR-324-3p 减少的这些有利影响。我们的研究证明了 miR-324-3p 对肺癌发展和进展的促进作用，从而为治疗这种破坏性疾病提供了新的靶点。我们发现这种相互作用上调了 NCAM1 的表达并激活了 MAPK 通路。抑制miR-324-3p可以抑制肺癌细胞的侵袭、迁移和自噬，延缓裸鼠皮下肿瘤的生长。ALX4 或 NCAM1 过表达的下调逆转了 miR-324-3p 减少的这些有利影响。我们的研究证明了 miR-324-3p 对肺癌发展和进展的促进作用，从而为治疗这种破坏性疾病提供了新的靶点。我们发现这种相互作用上调了 NCAM1 的表达并激活了 MAPK 通路。抑制miR-324-3p可以抑制肺癌细胞的侵袭、迁移和自噬，延缓裸鼠皮下肿瘤的生长。ALX4 或 NCAM1 过表达的下调逆转了 miR-324-3p 减少的这些有利影响。我们的研究证明了 miR-324-3p 对肺癌发展和进展的促进作用，从而为治疗这种破坏性疾病提供了新的靶点。ALX4 或 NCAM1 过表达的下调逆转了 miR-324-3p 减少的这些有利影响。我们的研究证明了 miR-324-3p 对肺癌发展和进展的促进作用，从而为治疗这种破坏性疾病提供了新的靶点。ALX4 或 NCAM1 过表达的下调逆转了 miR-324-3p 减少的这些有利影响。我们的研究证明了 miR-324-3p 对肺癌发展和进展的促进作用，从而为治疗这种破坏性疾病提供了新的靶点。