Yang Rui, Liu Gen, Han Limin, Qiu Yuheng, Wang Lulin, Wang Mei
Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
Front Oncol. 2021 Mar 15;11:616390. doi: 10.3389/fonc.2021.616390. eCollection 2021.
Gastric cancer (GC) is a common and invasive malignancy, which lacks effective treatment and is the third main reason of cancer death. Metabolic reprogramming is one of the main reasons that GC is difficult to treat in various environments. Particularly, abnormal glycolytic activity is the most common way of metabolism reprogramming in cancer cells. Numerous studies have shown that microRNAs play important roles in reprogramming glucose metabolism. Here, we found a microRNA-miR-365a-3p, was significantly downregulated in GC according to bioinformatics analysis. Low expression of miR-365a-3p correlated with poor prognosis of GC patients. Overexpression of miR-365a-3p in GC cells significantly inhibited cell proliferation by inducing cell cycle arrest at G1 phase. Notably, miR-365a-3p induced downregulation of HELLS through binding to its 3' untranslated region (UTR). Additionally, we found that miR-365a-3p suppressed aerobic glycolysis by inhibiting HELLS/GLUT1 axis. Lastly, we shown that overexpression of miR-365a-3p significantly inhibited tumor growth in nude mice. Conversely, Reconstituted the expression of HELLS rescued the suppressive effects of miR-365a-3p. Our data collectively indicated that miR-365a-3p functioned as a tumor suppressor in GC through downregulating HELLS. Therefore, targeting of the novel miR-365a-3p/HELLS axis could be a potentially effective therapeutic approach for GC.
胃癌（GC）是一种常见的侵袭性恶性肿瘤，缺乏有效的治疗方法，是癌症死亡的第三大主要原因。代谢重编程是GC在各种环境中难以治疗的主要原因之一。特别是，异常的糖酵解活性是癌细胞中代谢重编程最常见的方式。大量研究表明，微小RNA在葡萄糖代谢重编程中发挥重要作用。在此，根据生物信息学分析，我们发现一种微小RNA——miR-365a-3p在GC中显著下调。miR-365a-3p的低表达与GC患者的不良预后相关。在GC细胞中过表达miR-365a-3p通过诱导细胞周期停滞在G1期显著抑制细胞增殖。值得注意的是，miR-365a-3p通过与其3'非翻译区（UTR）结合诱导HELLS下调。此外，我们发现miR-365a-3p通过抑制HELLS/GLUT1轴抑制有氧糖酵解。最后，我们表明miR-365a-3p的过表达显著抑制裸鼠肿瘤生长。相反，恢复HELLS的表达可挽救miR-365a-3p的抑制作用。我们的数据共同表明，miR-365a-3p通过下调HELLS在GC中发挥肿瘤抑制作用。因此，靶向新的miR-365a-3p/HELLS轴可能是GC一种潜在有效的治疗方法。
