LINC00092 通过丙酮酸羧化酶介导的 AKT/mTOR 通路调节乳腺癌细胞的氧化应激和糖酵解。
LINC00092 Modulates Oxidative Stress and Glycolysis of Breast Cancer Cells via Pyruvate Carboxylase-Mediated AKT/mTOR Pathway.
机构信息
Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province 350001, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province 350001, China.
出版信息
Oxid Med Cell Longev. 2022 Jun 28;2022:5215748. doi: 10.1155/2022/5215748. eCollection 2022.
BACKGROUND
The discovery of noncoding RNAs (ncRNAs) offers new options for cancer-targeted therapy. This study is aimed at exploring the regulatory function of LINC00092 on breast cancer (BC) oxidative stress and glycolysis, along with internal mechanism concerning pyruvate carboxylase (PC).
METHODS
Bioinformatics analysis was used to explore LINC00092 (or friend leukemia virus integration 1 (FLI1)) expression on BC progression, as well as oxidative stress and glycolysis in BC. After LINC00092 overexpression or silence, BC cell viability, proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway were detected. Following 2-DG, SC79, or MK2206 treatment, effects of LINC00092 on BC cells were measured. Moreover, regulatory activity of LINC00092 in PC expression was analyzed. Whether PC participated in the modulation of LINC00092 on BC cell functions was explored.
RESULTS
LINC00092 was lowly expressed in BC and negatively related to BC progression. FLI1 bound to LINC00092 promoter to positively modulate LINC00092. LINC00092 overexpression inhibited BC cell proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway and likewise suppressed BC growth . Silence of LINC00092 had opposite influences. 2-DG partially reversed the LINC00092 silence-resulted increase of BC cell proliferation. SC79 alleviated the function of LINC00092 overexpression on BC cell functions. MK2206 had the contrary influence of SC79. Besides, LINC00092 bound to PC to modulate ubiquitination degradation of PC protein. PC took part in the influences of LINC00092 on BC cell functions.
CONCLUSIONS
LINC0092 modulates oxidative stress and glycolysis of BC cells via the PC-mediated AKT/mTOR pathway, which is possibly a target for BC diagnosis and therapy.
背景
非编码 RNA（ncRNA）的发现为癌症靶向治疗提供了新的选择。本研究旨在探讨 LINC00092 对乳腺癌（BC）氧化应激和糖酵解的调节功能，以及涉及丙酮酸羧化酶（PC）的内部机制。
方法
使用生物信息学分析来探讨 LINC00092（或 Friend 白血病病毒整合 1（FLI1））在 BC 进展过程中的表达，以及 BC 中的氧化应激和糖酵解。过表达或沉默 LINC00092 后，检测 BC 细胞活力、增殖、迁移、侵袭、氧化应激、糖酵解和 AKT/mTOR 通路。用 2-DG、SC79 或 MK2206 处理后，测量 LINC00092 对 BC 细胞的影响。此外，还分析了 LINC00092 对 PC 表达的调节活性。探讨了 PC 是否参与了 LINC00092 对 BC 细胞功能的调节。
结果
LINC00092 在 BC 中低表达，与 BC 进展呈负相关。FLI1 结合到 LINC00092 启动子上，正向调节 LINC00092。LINC00092 过表达抑制 BC 细胞增殖、迁移、侵袭、氧化应激、糖酵解和 AKT/mTOR 通路，同样抑制 BC 生长。沉默 LINC00092 则有相反的影响。2-DG 部分逆转了 LINC00092 沉默引起的 BC 细胞增殖增加。SC79 减轻了 LINC00092 过表达对 BC 细胞功能的影响。MK2206 的影响则与 SC79 相反。此外，LINC00092 与 PC 结合，调节 PC 蛋白的泛素化降解。PC 参与了 LINC00092 对 BC 细胞功能的影响。
结论
LINC0092 通过 PC 介导的 AKT/mTOR 通路调节 BC 细胞的氧化应激和糖酵解，这可能是 BC 诊断和治疗的一个靶点。
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