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（non-coding RNA），环状RNA（circular RNA, circRNA）在多种疾病与肿瘤中的作用已受到广泛关注。已有研究证实，环状RNA可通过多种分子机制参与急性髓系白血病（acute myeloid leukemia, AML）的疾病进展。然而，环状RNA在急性髓系白血病细胞增殖过程中的确切潜在分子机制仍尚不明确。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。实验结果显示，circCRKL在急性髓系白血病细胞系及临床样本中呈低表达水平。进一步研究发现，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则可增强上述细胞表型。此外，借助生物信息学工具与荧光素酶报告基因实验（luciferase assays），本研究证实circCRKL可通过海绵吸附miR-196a-5p与miR-196b-5p，上调p27的表达。进一步机制验证表明，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增殖，提示其或可成为急性髓系白血病治疗的潜在新靶点。