Li Zhouqiang, Zhang Hualing, Chen Zeshan, Wu Guanzhu, Guo Weixing, Li Yun
Second Ward, Department of Respiratory and Critical Care Medicine, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou, Guangxi 545000, P.R. China.
Department of Traditional Chinese Medicine, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, Guangxi 530016, P.R. China.
Int J Oncol. 2025 Aug;67(2). doi: 10.3892/ijo.2025.5773. Epub 2025 Jul 11.
In this review, the role of microRNA‑21 (miRNA‑21) as an oncogene in lung cancer was investigated. Studies have shown that miRNA‑21 can promote the progression of lung cancer by targeting downstream target genes, and its expression can be modulated by transcription factors, DNA methylation or competitive endogenous RNA as an upstream regulator. This review highlights that miRNA‑21 can promote the progression of lung cancer through multiple signaling pathways, with a focus on the PI3K/AKT, MEK/ERK, TGF‑β/SMAD, Hippo, NF‑κB and STAT3 signaling pathways. Mechanistically, miRNA‑21 plays an important role in the progression of lung cancer by regulating multiple biological processes, such as proliferation, invasion, metastasis, apoptosis and angiogenesis in lung cancer cells. Higher expression of miRNA‑21 is associated with chemotherapy, radiotherapy and immune resistance in lung cancer. Targeting these molecular pathways may be a novel therapeutic strategy for treating lung cancer. Additionally, miRNA‑21 can serve as a biomarker for lung cancer diagnosis, prognosis and treatment response. This review also summarized the following: i) Current methods employed to inhibit the expression of miRNA‑21 in lung cancer, including CRISPR/Cas9 technology; ii) the application of natural anticancer agents, oligonucleotides, small molecules and miRNA sponges; and iii) the nano‑delivery systems developed for miRNA‑21 inhibitors. Finally, the advancements in research on miRNA mimics and inhibitors in clinical trials, which may promote the application of miRNA‑21 in clinical trials in lung cancer, were discussed. Given that lung cancer is a considerable public health challenge, these studies provide new ways of treating patients with lung cancer.
在本综述中，研究了微小RNA-21（miRNA-21）作为肺癌癌基因的作用。研究表明，miRNA-21可通过靶向下游靶基因促进肺癌进展，其表达可受转录因子、DNA甲基化或作为上游调节因子的竞争性内源性RNA调控。本综述强调，miRNA-21可通过多种信号通路促进肺癌进展，重点关注PI3K/AKT、MEK/ERK、TGF-β/SMAD、Hippo、NF-κB和STAT3信号通路。从机制上讲，miRNA-21通过调节肺癌细胞的增殖、侵袭、转移、凋亡和血管生成等多种生物学过程，在肺癌进展中发挥重要作用。miRNA-21的高表达与肺癌的化疗、放疗和免疫抵抗相关。靶向这些分子通路可能是治疗肺癌的一种新的治疗策略。此外，miRNA-21可作为肺癌诊断、预后和治疗反应的生物标志物。本综述还总结了以下内容：i）目前用于抑制肺癌中miRNA-21表达的方法，包括CRISPR/Cas9技术；ii）天然抗癌剂、寡核苷酸、小分子和miRNA海绵的应用；iii）为miRNA-21抑制剂开发的纳米递送系统。最后，讨论了miRNA模拟物和抑制剂在临床试验中的研究进展，这可能会促进miRNA-21在肺癌临床试验中的应用。鉴于肺癌是一个重大的公共卫生挑战，这些研究为肺癌患者的治疗提供了新的途径。
