Circular RNA circCRKL inhibits the proliferation of acute myeloid leukemia cells via the miR-196a-5p/miR-196b-5p/p27 axis

As a new type of non-coding RNA, the role of circular RNA (circRNA) in various diseases and tumors has received considerable attention. Studies have shown that circRNAs play an important role in the progression of acute myeloid leukemia (AML) via different mechanisms. However, the specific underlying molecular mechanism of circRNAs in the proliferation of AML cells remians unclear. This study aimed to clarify the biological role and mechanism of circCRKL in AML. The results indicated low circCRKL expression in AML cell lines and samples. Moreover, the overexpression of circCRKL inhibited the proliferation and colony-forming ability of AML cells, while its silencing promoted them. In addition, bioinformatics tools and luciferase assays revealed that circCRKL could sponge miR-196a-5p and miR-196b-5p to promote the expression of p27. Furthermore, circCRKL inhibited AML cell proliferation via the miR-196a-5p/miR-196b-5p/p27 axis, suggesting a potential new target for AML therapy.

作为一类新型非编码RNA，环状RNA（circular RNA, circRNA）在多种疾病及肿瘤中的作用已受到广泛关注。已有研究证实，环状RNA可通过多种机制在急性髓系白血病（acute myeloid leukemia, AML）的进展中发挥重要作用。然而，环状RNA在急性髓系白血病细胞增殖过程中的确切分子机制仍不明确。本研究旨在阐明circCRKL在急性髓系白血病中的生物学功能及作用机制。研究结果显示，circCRKL在急性髓系白血病细胞系及临床样本中呈低表达水平。进一步实验发现，过表达circCRKL可抑制急性髓系白血病细胞的增殖与集落形成能力，而敲低circCRKL则可促进上述过程。此外，通过生物信息学工具与荧光素酶实验（luciferase assays）证实，circCRKL可通过分子海绵作用吸附miR-196a-5p与miR-196b-5p，从而上调p27的表达。机制研究表明，circCRKL可通过miR-196a-5p/miR-196b-5p/p27信号轴抑制急性髓系白血病细胞的增殖，这为急性髓系白血病的治疗提供了潜在新靶点。