Department of Otorhinolaryngology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
PeerJ. 2023 Oct 2;11:e16140. doi: 10.7717/peerj.16140. eCollection 2023.
Metabolic reprogramming is a key marker in the occurrence and development of tumors. This process generates more reactive oxygen species (ROS), promoting the development of oxidative stress. To prevent ROS from harming tumor cells, tumor cells can increase the production of reducing agents to counteract excessive ROS. has been shown to promote the production of reductive mRNA and plays an important role in the process of oxidative stress.
In this study, the clinical data and RNA sequencing of head and neck tumors were obtained from The Cancer Genome Atlas data set. The long non-coding RNA (LncRNA) related to oxidative stress were then identified using differential and correlation analyses. The differential expression and prognosis of the identified lncRNA were then verified using samples from the library of the Second Hospital of Hebei Medical University. Only was substantially expressed in cancer tissues and predicted a poor prognosis. The tumor-promoting impact of was then confirmed using functional assays. The data set was then split into high- and low-expression subgroups based on the median gene expression of to obtain the mRNA that had a large difference between the two groups, and examine the mechanism of on GPX2 using quantitative real-time PCR, RNA binding protein immunoprecipitation assay, and chromatin immunoprecipitation. Mass spectrometry was used to identify -binding proteins and western blotting was used to investigate probable mechanisms.
The lncRNA is associated with oxidative stress in head and neck tumors. functional assays showed that the gene has a cancer-promoting effect, increasing lactic acid and superoxide dismutase production, and reducing the production of ROS and malondialdehyde. promotes the transcription of GPX2 by binding to transcription factor Nrf2. The gene also inhibits the degradation of ENO1, a crucial enzyme in glycolysis, by binding to protein ENO1.
This study shows that can promote glycolysis and reduce the harm to tumor cells caused by ROS. The gene can also be used as a possible target for the treatment of head and neck tumors.
代谢重编程是肿瘤发生和发展的一个关键标志。这个过程会产生更多的活性氧（ROS），促进氧化应激的发展。为了防止 ROS 伤害肿瘤细胞，肿瘤细胞可以增加还原剂的产生来对抗过多的 ROS。 已被证明可以促进还原性 mRNA 的产生，并在氧化应激过程中发挥重要作用。
本研究从癌症基因组图谱数据集获得了头颈部肿瘤的临床数据和 RNA 测序。然后使用差异和相关性分析来鉴定与氧化应激相关的长非编码 RNA（lncRNA）。然后使用河北医科大学第二医院文库中的样本验证了鉴定的 lncRNA 的差异表达和预后。只有 在癌症组织中大量表达，并预测预后不良。然后使用 功能测定法证实了 的肿瘤促进作用。根据 的中位基因表达将数据集分为高表达和低表达亚组，以获得两组之间差异较大的 mRNA，并使用定量实时 PCR、RNA 结合蛋白免疫沉淀测定和染色质免疫沉淀检测 对 GPX2 的作用机制。使用质谱法鉴定 -结合蛋白，并使用 Western blot 法研究可能的机制。
lncRNA 与头颈部肿瘤中的氧化应激有关。 功能测定表明，该基因具有致癌作用，可增加乳酸和超氧化物歧化酶的产生，并减少 ROS 和丙二醛的产生。 通过与转录因子 Nrf2 结合来促进 GPX2 的转录。该基因还通过与糖酵解关键酶 ENO1 结合来抑制 ENO1 的降解。
本研究表明， 可以促进糖酵解并减少 ROS 对肿瘤细胞的伤害。该基因也可以作为治疗头颈部肿瘤的潜在靶点。
