Yuan Tao, Liu Haiyan, Li Fangfang, Meng Qingyue, Wang Yajuan, Yuan Mei
Hospital Office, The No. 3 People's Hospital of Qingdao, Qingdao, China.
Department of Dermatology, The No. 8 People's Hospital of Qingdao, Qingdao, China.
Transl Cancer Res. 2025 Feb 28;14(2):1375-1387. doi: 10.21037/tcr-2025-8. Epub 2025 Feb 26.
Gastric cancer (GC) is a leading cause of cancer-related death. MicroRNAs (miRNAs or miRs) play a crucial role in the pathology of GC, including cell proliferation, invasion, and metastasis. In this study, genes targeted by miR-155-5p were predicted using bioinformatic tools. We found that the expression of miR-155-5p in GC cell lines differed relative to the expression of F-box protein 11 (), which is involved in the regulation of cellular processes. This study sought to examine the function of miR-155-5p and the precise mechanism underlying its regulatory function in modulating proliferation and apoptosis in GC.
The luciferase reporter assay results showed that miR-155-5p bound directly to the three prime untranslated region (3'-UTR) of , which further downregulated expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western-blot analyses confirmed that miR-155-5p negatively regulated the messenger RNA (mRNA) and protein expression of . The effects of on cell proliferation and apoptosis in GC cell lines was further examined using Cell Counting Kit-8 (CCK-8) and flow cytometry.
We found that promoted proliferation and decreased apoptosis in GC cells. Conversely, rescue experiments showed that the knockdown of limited the effects of miR-155-5p on the proliferation and apoptosis of GC cells, providing further evidence that is a functional target of miR-155-5p. Further, the overexpression of miR-155-5p inhibited cell growth via the targeted inhibition of that regulated mammalian target of rapamycin (mTOR) signaling pathway in the GC cells.
Overall, these results showed that miR-155-5p may serve as a tumor suppressor in GC and that the miR-155-5p/ axis regulates tumor progression via the mTOR signaling pathway. Consequently, our findings may lead to the development a novel treatment strategy for GC.
胃癌（GC）是癌症相关死亡的主要原因。微小RNA（miRNA或miR）在胃癌的病理过程中发挥着关键作用，包括细胞增殖、侵袭和转移。在本研究中，使用生物信息学工具预测了miR-155-5p靶向的基因。我们发现，与参与细胞过程调节的F-box蛋白11（）的表达相比，miR-155-5p在胃癌细胞系中的表达有所不同。本研究旨在探讨miR-155-5p的功能及其在调节胃癌细胞增殖和凋亡中发挥调节作用的精确机制。
荧光素酶报告基因检测结果表明，miR-155-5p直接与的3'非翻译区（3'-UTR）结合，进而下调的表达。定量逆转录-聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析证实，miR-155-5p负向调节的信使核糖核酸（mRNA）和蛋白质表达。使用细胞计数试剂盒-8（CCK-8）和流式细胞术进一步检测了对胃癌细胞系细胞增殖和凋亡的影响。
我们发现促进胃癌细胞增殖并减少其凋亡。相反，挽救实验表明，敲低可限制miR-155-5p对胃癌细胞增殖和凋亡的影响，进一步证明是miR-155-5p的功能靶点。此外，miR-155-5p的过表达通过靶向抑制调节胃癌细胞中雷帕霉素靶蛋白（mTOR）信号通路的来抑制细胞生长。
总体而言，这些结果表明miR-155-5p可能作为胃癌中的肿瘤抑制因子，并且miR-155-5p/轴通过mTOR信号通路调节肿瘤进展。因此，我们的发现可能会导致开发一种新的胃癌治疗策略。
