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BACKGROUND: With the development of high-throughput technology, non-coding RNAs have gradually attracted attention and are widely involved in the course of various respiratory diseases. The progression of idiopathic pulmonary fibrosis is accompanied by stem cell abnormality and recent studies have shown that non-coding RNAs are associated with stem cell abnormality, thus affecting the progression of pulmonary fibrosis. Gene therapy that targets non-coding RNAs hints at the possibility of blocking the fibrosis process. OBJECTIVE: To summarize the research progress of non-coding RNAs in stem cell dysfunction and treatment of idiopathic pulmonary fibrosis. METHODS: English search terms included “IPF, stem cells, miRNA, lncRNA, circRNA, treatment” and Chinese search terms contained “idiopathic pulmonary fibrosis, stem cells, miRNA, lncRNA, circRNA, treatment”. Databases including PubMed, Wiley InterScience, CNKI, and Wanfang were used for retrieval, covering articles in the past decade. Screening was performed based on the inclusion and exclusion criteria. Finally, 82 articles were included for analysis. RESULTS AND CONCLUSION: (1) The recent studies on the correlation between non-coding RNAs and the mechanisms of stem cell abnormality in idiopathic pulmonary fibrosis were summarized, revealing that miRNAs, lncRNAs, and circRNAs jointly regulate the abnormal activation and differentiation of stem cells, and miRNAs are often the central link of the mechanisms of lncRNAs and circRNAs. (2) Existing trials have confirmed the safety of transplantation therapy to a certain extent, but in terms of efficacy, the diffusion function of patients has only been slightly improved, but the degree of fibrosis has not been significantly alleviated. Most importantly, the trials were non-randomized and lack of placebo controls, so more placebo-controlled randomized trials are needed. (3) The most important advantage of non-coding RNA-targeted gene therapy is that it has the characteristics of multi-gene regulation, which can intervene stem cell abnormalities from the upstream pathways. Based on the breakthroughs made in vivo and in vitro research, non-coding RNAs have been confirmed to be related to the targets of several drugs for idiopathic pulmonary fibrosis. (4) However, the disadvantages of gene therapy include that it still can only produce short-term effects, and it also faces problems such as effective dose, drug stability, and delivery in the human body. These problems need to be further resolved by future research. (5) In conclusion, although non-coding RNA-targeted therapy is difficult, it can be regarded as a novel way to improve the abnormality of stem cells in idiopathic pulmonary fibrosis, and combining this therapy with stem cell transplantation may achieve better efficacy. [ABSTRACT FROM AUTHOR]

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