Department of Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China.
Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi 046000, Shanxi, China.
Aging (Albany NY). 2023 Mar 30;15(7):2525-2540. doi: 10.18632/aging.204623.
As a well-established member of a strongly conserved protein family, DDX5 binds to RNA helicase in a specific manner, which can regulate mRNA transcription, protein translation and synthesis and precursor messenger RNA processing or alternative splicing. The effects of DDX5 on carcinogenesis and cancer progression are increasingly evident. Circular RNAs (circRNAs), a novel group of functionally non-coding RNAs (ncRNAs) with disordered expression, are associated with various pathological processes (e.g., tumors). circRNA pattern and its function regulated by DDX5 have not yet been determined. According to our findings, DDX5 was dramatically upregulated for stomach cancer tissues, and its overexpression contributed to the cell growth and invasion of GC cells. Based on the analysis of genome-wide circRNAs conducted with circRNA sequencing, DDX5 induces a large number of circRNAs. Further to screen several circRNAs from PHF14 for function, it was found that circPHF14 was essential for the growth and tumorigenesis of DDX5-positive gastric cancer cells. These findings suggest that in addition to the messenger RNA and microRNA patterns, DDX5 also effects a circRNA pattern, as demonstrated by circPHF14. DDX5-induced circRNAs have been found to be of crucial importance for the growth of DDX5-positive gastric cancer cells, providing a new therapeutic target.
作为一个功能强大的高度保守的蛋白家族的成熟成员，DDX5 以特定的方式与 RNA 解旋酶结合，从而可以调节 mRNA 转录、蛋白质翻译和合成以及前体信使 RNA 加工或选择性剪接。DDX5 对肿瘤发生和癌症进展的影响越来越明显。环状 RNA（circRNA）是一类具有无序表达的新型功能非编码 RNA（ncRNA），与各种病理过程（如肿瘤）有关。DDX5 调控的 circRNA 模式及其功能尚未确定。根据我们的研究结果，DDX5 在胃癌组织中显著上调，其过表达促进 GC 细胞的生长和侵袭。基于 circRNA 测序进行的全基因组 circRNA 分析表明，DDX5 诱导大量 circRNA。进一步从 PHF14 筛选出几种 circRNA 进行功能分析，发现 circPHF14 对 DDX5 阳性胃癌细胞的生长和致瘤性是必需的。这些发现表明，除了信使 RNA 和 microRNA 模式外，DDX5 还通过 circPHF14 影响 circRNA 模式。DDX5 诱导的 circRNA 对于 DDX5 阳性胃癌细胞的生长至关重要，为治疗提供了新的靶点。
