Ye Chen, Jiang Sihan, Zeng Tanlun, He Shaohui, Cao Jinjin, Xiao Jianru
School of Health Science and Technology, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai, 200093, China.
Spinal Tumor Center, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Discov Oncol. 2024 Jun 26;15(1):245. doi: 10.1007/s12672-024-01107-9.
LOXL2, an enzyme belonging to the LOX family, facilitates the cross-linking of extracellular matrix (ECM) elements. However, the roles of the LOXL2 gene in mechanisms of oncogenesis and tumor development have not been clearly defined. In this pan-cancer study, we examined the notable disparity in LOXL2 expression at the mRNA and protein levels among various cancer types and elucidated its interconnected roles in tumor progression, mutational profile, immune response, and cellular senescence. Apart from investigating the hyperexpression of LOXL2 being related to poorer prognosis in different types of tumors, this study also unveiled noteworthy connections between LOXL2 and genetic mutations, infiltration of tumor immune cells, and genes in immune checkpoint pathways. Further analysis revealed the participation of LOXL2 in multiple pathways related to cancer extracellular matrix remodeling and cellular senescence. Moreover, our investigation uncovered that the knockdown and inhibition of LOXL2 significantly attenuated the proliferation and migration of PC-9 and HCC-LM3 cells. The knock-down and inhibition of LOXL2 enhanced cellular senescence in lung and liver cancer cells, as confirmed by SA-β-Gal staining and quantitative RT-PCR analyses. This comprehensive analysis offers valuable insights on the functions of LOXL2 in different types of cancer and its role in regulating the senescence of cancer cells.
赖氨酰氧化酶样蛋白2（LOXL2）是一种属于赖氨酰氧化酶（LOX）家族的酶，可促进细胞外基质（ECM）成分的交联。然而，LOXL2基因在肿瘤发生和肿瘤发展机制中的作用尚未明确界定。在这项泛癌研究中，我们研究了不同癌症类型中LOXL2在mRNA和蛋白质水平表达的显著差异，并阐明了其在肿瘤进展、突变谱、免疫反应和细胞衰老中的相互关联作用。除了研究LOXL2的高表达与不同类型肿瘤预后较差有关外，本研究还揭示了LOXL2与基因突变、肿瘤免疫细胞浸润以及免疫检查点途径中的基因之间的显著联系。进一步分析表明，LOXL2参与了与癌症细胞外基质重塑和细胞衰老相关的多种途径。此外，我们的研究发现，敲低和抑制LOXL2可显著减弱PC-9和HCC-LM3细胞的增殖和迁移。如SA-β-Gal染色和定量RT-PCR分析所证实，敲低和抑制LOXL2可增强肺癌和肝癌细胞的细胞衰老。这项综合分析为LOXL2在不同类型癌症中的功能及其在调节癌细胞衰老中的作用提供了有价值的见解。
