Liu Zhenyang, Wang Junyu, Li Yunjun, Fan Juan, Chen Lihua, Xu Ruxiang
1 Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
2 Department of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Tumour Biol. 2017 Feb;39(2):1010428317691429. doi: 10.1177/1010428317691429.
Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.
胶质母细胞瘤是恶性胶质瘤最具侵袭性的表现形式，被认为是人类癌症中最致命的类型之一。研究发现，微小RNA紧密调控多种生物学过程，并在癌症病因学中发挥重要作用。在本研究中，我们发现与配对的非肿瘤组织以及胶质母细胞瘤细胞系相比，微小RNA - 153在胶质母细胞瘤组织中显著下调。为了研究微小RNA - 153在胶质母细胞瘤中的潜在功能，我们用合成的微小RNA - 153寡核苷酸转染胶质母细胞瘤细胞系U87MG以及U373MG，观察到细胞增殖减少且凋亡增加。我们进一步发现微小RNA - 153抑制谷氨酰胺利用和谷氨酸生成。生物信息学分析显示，催化谷氨酰胺形成谷氨酸的谷氨酰胺酶是微小RNA - 153的潜在靶点。事实上，当谷氨酰胺酶被敲低时，微小RNA - 153不能进一步降低谷氨酰胺利用。谷氨酰胺酶的过表达消除了微小RNA - 153对谷氨酰胺利用的影响。此外，胶质母细胞瘤与配对的非肿瘤组织中微小RNA - 153和谷氨酰胺酶的相对表达呈负相关，进一步表明微小RNA - 153可能在体内负向调节谷氨酰胺酶。这些结果证明了微小RNA - 153在调节谷氨酰胺代谢中的意外作用，并强化了微小RNA - 153作为胶质母细胞瘤治疗靶点的作用。
