Department of Science Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea.
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, GA 30322, USA.
Int J Mol Sci. 2022 Nov 26;23(23):14808. doi: 10.3390/ijms232314808.
Metabolic alterations that support the supply of biosynthetic molecules necessary for rapid and sustained proliferation are characteristic of cancer. Some cancer cells rely on glutamine to maintain their energy requirements for growth. Glutamine is an important metabolite in cells because it not only links to the tricarboxylic acid cycle by producing α-ketoglutarate by glutaminase and glutamate dehydrogenase but also supplies other non-essential amino acids, fatty acids, and components of nucleotide synthesis. Altered glutamine metabolism is associated with cancer cell survival, proliferation, metastasis, and aggression. Furthermore, altered glutamine metabolism is known to be involved in therapeutic resistance. In recent studies, lncRNAs were shown to act on amino acid transporters and glutamine-metabolic enzymes, resulting in the regulation of glutamine metabolism. The lncRNAs involved in the expression of the transporters include the abhydrolase domain containing 11 antisense RNA 1, LINC00857, plasmacytoma variant translocation 1, Myc-induced long non-coding RNA, and opa interacting protein 5 antisense RNA 1, all of which play oncogenic roles. When it comes to the regulation of glutamine-metabolic enzymes, several lncRNAs, including nuclear paraspeckle assembly transcript 1, XLOC_006390, urothelial cancer associated 1, and thymopoietin antisense RNA 1, show oncogenic activities, and others such as antisense lncRNA of glutaminase, lincRNA-p21, and ataxin 8 opposite strand serve as tumor suppressors. In addition, glutamine-dependent cancer cells with lncRNA dysregulation promote cell survival, proliferation, and metastasis by increasing chemo- and radio-resistance. Therefore, understanding the roles of lncRNAs in glutamine metabolism will be helpful for the establishment of therapeutic strategies for glutamine-dependent cancer patients.
支持快速和持续增殖所需生物合成分子供应的代谢改变是癌症的特征。一些癌细胞依赖谷氨酰胺来维持其生长的能量需求。谷氨酰胺是细胞中的一种重要代谢物，因为它不仅通过谷氨酰胺酶和谷氨酸脱氢酶产生α-酮戊二酸与三羧酸循环相连，还提供其他非必需氨基酸、脂肪酸和核苷酸合成的成分。改变的谷氨酰胺代谢与癌细胞的存活、增殖、转移和侵袭有关。此外，改变的谷氨酰胺代谢与治疗抵抗有关。在最近的研究中，lncRNAs 被证明作用于氨基酸转运体和谷氨酰胺代谢酶，从而调节谷氨酰胺代谢。涉及转运体表达的 lncRNAs 包括 abhydrolase 结构域包含 11 反义 RNA 1、LINC00857、浆细胞瘤变体易位 1、Myc 诱导的长非编码 RNA 和 opa 相互作用蛋白 5 反义 RNA 1，它们都发挥致癌作用。当涉及到谷氨酰胺代谢酶的调节时，几种 lncRNAs，包括核斑形成转录物 1、XLOC_006390、尿路上皮癌相关 1 和胸肽素反义 RNA 1，表现出致癌活性，而其他如谷氨酰胺酶的反义 lncRNA、lincRNA-p21 和 ataxin 8 反义链则作为肿瘤抑制物。此外，lncRNA 失调的谷氨酰胺依赖性癌细胞通过增加化疗和放疗耐药性来促进细胞存活、增殖和转移。因此，了解 lncRNAs 在谷氨酰胺代谢中的作用将有助于为谷氨酰胺依赖性癌症患者建立治疗策略。
