Human antigen R (HuR), also known as ELAVL1, is a widely expressed RNA-binding protein (RBP) that has a significant impact on the development and advancement of tumors. Our previous study found that 5-fluorouracil (5-FU) may impede the proliferation and increase apoptosis in gastric cancer cells by reducing the nucleocytoplasmic shuttling of HuR. However, how posttranscriptional regulation influences HuR functions in gastric cancer remains to be elucidated. Here, we demonstrated that miR-325-3p has the potential to regulate the expression level of HuR by directly binding to its 3′UTR, which in turn led to a significant reduction in proliferation and an increase in apoptosis in gastric cancer cells. In addition, xenograft experiment showed that knockdown of HuR or overexpression of miR-325-3p group exhibited smaller tumor sizes after transplant of gastric cancer cells into zebrafish larvae. Thus, our findings offer new insights into the pathogenesis of gastric cancer and may potentially assist in identifying novel targets for drug therapy.

中文翻译：

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miR-325-3p通过抑制人抗原R减少胃癌细胞增殖并促进其凋亡

人类抗原R（HuR），也称为ELAVL1，是一种广泛表达的RNA结合蛋白（RBP），对肿瘤的发生和进展具有显着影响。我们前期的研究发现，5-氟尿嘧啶（5-FU）可能通过减少HuR的核质穿梭来阻碍胃癌细胞的增殖并增加细胞凋亡。然而，转录后调控如何影响胃癌中的 HuR 功能仍有待阐明。在这里，我们证明miR-325-3p有可能通过直接结合HuR的3'UTR来调节HuR的表达水平，从而导致胃癌细胞的增殖显着减少和细胞凋亡增加。此外，异种移植实验表明，敲低HuR或过表达miR-325-3p组将胃癌细胞移植到斑马鱼幼虫中后，肿瘤尺寸更小。因此，我们的研究结果为胃癌的发病机制提供了新的见解，并可能有助于确定药物治疗的新靶点。