Tang Xiaogen, Lei Tingting, Huang Boya, Wu Guangjie, Tian Yizhen, Xiang Jian, Fu Dongwei, Zhang Hongyi
Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Front Oncol. 2025 Apr 28;15:1560954. doi: 10.3389/fonc.2025.1560954. eCollection 2025.
Melanoma brain metastasis is an lethal event. Investigating the molecules that potentially promoted melanoma metastasis is important for targeted therapy.
The transcriptional profiles of totaling 7 melanoma samples, including 4 primary and 3 brain metastatic tissues were studied on the single-cell RNA sequencing level, and the expression of PLEKHA5 was examined in tumor clusters. Then PLEKHA5 expression was validated in brain Metastatic model by left ventricular injections in nude mice. The functional effect of PLEKHA5 isoforms (Long or Short) on proliferation and migration of melanoma was studied by RNA interference, overexpression by lentivirus vector, CCK8 test, colony formation test, transwell chamber assay. The targets and signal pathways that was potentially regulated by PLEKHA5 was studied by RNA-sequencing.
PLEKHA5 expression increased in brain metastatic melanoma at single cell level. PLEKH5 was constantly upregulated in brain metastatic tissue of melanoma in animal model. PLEKHA5-L had the potential for melanoma migration and proliferation by upregulating oncogenes such as HRAS, AKT3 etc. PLEKHA5-L also upregulated expression of PD-L1 and ABC transporters that were associated with therapy resistant.
PLEKHA5-L was potential therapeutic target for metastatic melanoma.
黑色素瘤脑转移是一种致命事件。研究潜在促进黑色素瘤转移的分子对于靶向治疗很重要。
在单细胞RNA测序水平上研究了总共7个黑色素瘤样本的转录谱，包括4个原发性和3个脑转移组织，并在肿瘤簇中检测了PLEKHA5的表达。然后通过裸鼠左心室注射在脑转移模型中验证了PLEKHA5的表达。通过RNA干扰、慢病毒载体过表达、CCK8试验、集落形成试验、Transwell小室试验研究了PLEKHA5异构体（长或短）对黑色素瘤增殖和迁移的功能作用。通过RNA测序研究了可能受PLEKHA5调控的靶点和信号通路。
在单细胞水平上，脑转移黑色素瘤中PLEKHA5表达增加。在动物模型中，黑色素瘤脑转移组织中PLEKH5持续上调。PLEKHA5-L通过上调HRAS、AKT3等癌基因具有促进黑色素瘤迁移和增殖的潜力。PLEKHA5-L还上调了与治疗抗性相关的PD-L1和ABC转运蛋白的表达。
PLEKHA5-L是转移性黑色素瘤的潜在治疗靶点。
