Center for Rehabilitation Medicine, Cancer Center, Department of Orthopedics, Zhejiang Provincial People’s Hospital affiliated to Qingdao University, Qingdao, Shandong, China.
Center for Rehabilitation Medicine, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Aging (Albany NY). 2023 Oct 12;15(19):10640-10680. doi: 10.18632/aging.205104.
As a member of the mitochondrial ribosomal protein family, mitochondrial ribosomal protein L13 (MRPL13) is responsible for synthesizing mitochondrial proteins in cells. Several studies have indicated that MRPL13 is associated with the proliferation cycle, migration ability, apoptosis and autophagy of cancer cells. However, a thorough examination of MRPL13 across cancers remains uncertain. Therefore, we tried to clarify the relationship between MRPL13 and pan-cancer, and verified it in lung adenocarcinoma by various methods. Finally, our research is expected to reveal new targets for pan-cancer treatment and improve the prognosis of cancer patients.
Using bioinformatics tools, we quantified the differential expression of MRPL13 between cancer tissues and corresponding or noncorresponding normal tissues across cancers. We also analyzed the relationships between MRPL13 expression levels and several factors, including diagnosis, prognosis, mutation, functional signaling pathways, immune infiltration, RNA modification, and the relationship with cuproptosis-related genes. Furthermore, we studied the relationship between the expression level of MRPL13 across cancers and the change in cancer functional status through single-cell data. In addition, quantitative experiments (PCR and Western blot) proved that the expression of MRPL13 was significantly different between LUAD and control samples. Finally, the effect of knocking out MRPL13 on cancer cells was compared by gene silencing experiments. In summary, we used a combination of bioinformatics and experimental applications to study the potential roles of MRPL13 in cancer.
After conducting a multidimensional analysis, we found that the application of MRPL13 multigroup analysis can effectively improve the diagnostic efficiency of various cancers and predict the prognosis of cancer. Moreover, MRPL13 in pan-cancer is related to the cancer immune infiltration pattern, methylation level and cuproptosis-related genes. Furthermore, single-cell data analysis showed that the modules of metastasis, EMT, cell cycle, DNA repair, invasion, DNA damage and proliferation were positively correlated with the expression of MRPL13 in LUAD (Lung adenocarcinoma), while the modules of hypoxia and inflammation were negatively correlated. Moreover, through quantitative experiments, we observed higher expression of MRPL13 in cancer tissues at the RNA or protein level. Knockdown of MRPL13 in LUAD led to decreased cancer cell survival, delayed tumor division and migration, reduced invasion, and increased cancer cell apoptosis.
Our study demonstrates the potential of using MRPL13 as a molecular biomarker for diagnosing and suggesting the prognosis of certain malignant tumors. Furthermore, our research shows that MRPL13 may be an effective therapeutic target for lung adenocarcinoma.
作为线粒体核糖体蛋白家族的一员，线粒体核糖体蛋白 L13（MRPL13）负责在细胞内合成线粒体蛋白。多项研究表明，MRPL13 与癌细胞的增殖周期、迁移能力、凋亡和自噬有关。然而，对 MRPL13 在各种癌症中的全面研究仍不确定。因此，我们试图阐明 MRPL13 与泛癌之间的关系，并通过各种方法在肺腺癌中进行验证。最终，我们的研究有望为泛癌治疗揭示新的靶点，并改善癌症患者的预后。
使用生物信息学工具，我们定量分析了癌症组织与相应或不相应正常组织之间 MRPL13 的差异表达。我们还分析了 MRPL13 表达水平与多个因素之间的关系，包括诊断、预后、突变、功能信号通路、免疫浸润、RNA 修饰以及与铜死亡相关基因的关系。此外，我们通过单细胞数据研究了跨癌症的 MRPL13 表达水平与癌症功能状态变化之间的关系。此外，定量实验（PCR 和 Western blot）证明了 LUAD 和对照样本之间 MRPL13 表达水平的显著差异。最后，通过基因沉默实验比较了敲除 MRPL13 对癌细胞的影响。总之，我们结合生物信息学和实验应用来研究 MRPL13 在癌症中的潜在作用。
经过多维分析，我们发现应用 MRPL13 多组分析可以有效提高各种癌症的诊断效率，并预测癌症的预后。此外，泛癌中的 MRPL13 与癌症免疫浸润模式、甲基化水平和铜死亡相关基因有关。此外，单细胞数据分析表明，LUAD（肺腺癌）中转移、EMT、细胞周期、DNA 修复、侵袭、DNA 损伤和增殖模块与 MRPL13 的表达呈正相关，而缺氧和炎症模块呈负相关。此外，通过定量实验，我们观察到癌症组织中 MRPL13 在 RNA 或蛋白质水平上的表达较高。在 LUAD 中敲低 MRPL13 导致癌细胞存活率降低、肿瘤分裂和迁移延迟、侵袭减少以及癌细胞凋亡增加。
我们的研究表明，MRPL13 有潜力作为诊断某些恶性肿瘤的分子生物标志物，并提示预后。此外，我们的研究表明，MRPL13 可能是肺腺癌的有效治疗靶点。
