Wu Xinrong, Li Yifan, Wang Weiwei, Xu Jiale, Zhao Bei, Sun Wenqi, Ge Dan, Xiong Longying, Dou Xiaotan, Zou Xiaoping, Wang Lei, Chen Min
Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China.
Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Jiangsu, 210000, China.
Sci Rep. 2025 Jan 28;15(1):3542. doi: 10.1038/s41598-025-87389-7.
Gastric cancer (GC) is a prevalent malignant tumor of the digestive system that is often diagnosed at advanced stages owing to inconspicuous early symptoms and a lack of specific examination methods. Effective treatment of advanced stages remains challenging, emphasizing the need for new therapeutic targets. Metabolic reprogramming, a hallmark of tumors, plays a pivotal role in tumor progression, immune evasion, and immune surveillance. DNA damage-regulated autophagy modulator 1 (DRAM1) encodes a hexameric transmembrane protein that is predominantly located in lysosomes and induces autophagy; however, its mechanism of action in gastric cancer remains unclear. Our study found that elevated DRAM1 expression in patients with GC correlated with survival and prognosis. DRAM1 knockdown suppressed energy metabolism in GC cells through the PI3K/AKT/mTOR signaling pathway, thereby mitigating GC progression. Atorvastatin, a focus of recent tumor research, significantly enhanced apoptosis levels in DRAM1 knockdown GC cells compared to the control group. Therefore, through metabolic reprogramming, DRAM1 may serve as a potential therapeutic target for GC prevention.
胃癌（GC）是一种常见的消化系统恶性肿瘤，由于早期症状不明显且缺乏特异性检查方法，往往在晚期才被诊断出来。晚期胃癌的有效治疗仍然具有挑战性，这凸显了寻找新治疗靶点的必要性。代谢重编程作为肿瘤的一个标志，在肿瘤进展、免疫逃逸和免疫监视中起着关键作用。DNA损伤调节自噬调节剂1（DRAM1）编码一种主要位于溶酶体的六聚体跨膜蛋白，并诱导自噬；然而，其在胃癌中的作用机制仍不清楚。我们的研究发现，GC患者DRAM1表达升高与生存和预后相关。敲低DRAM1可通过PI3K/AKT/mTOR信号通路抑制GC细胞的能量代谢，从而减缓GC进展。阿托伐他汀是近期肿瘤研究的一个热点，与对照组相比，它能显著提高敲低DRAM1的GC细胞的凋亡水平。因此，通过代谢重编程，DRAM1可能成为预防GC的潜在治疗靶点。
