He WenFeng, Yang Gang, Liu Shuya, Maghsoudloo Mazaher, Shasaltaneh Marzieh Dehghan, Kaboli Parham Jabbarzadeh, Zhang Cuiwei, Zhang JingHeng, Entezari Maliheh, Imani Saber, Wen QingLian
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China; Department of Oncology, Anyue Hospital of Traditional Chinese Medicine, Second Ziyang Hospital of Traditional Chinese Medicine, Ziyang, Sichuan, China.
Transl Oncol. 2021 Dec;14(12):101237. doi: 10.1016/j.tranon.2021.101237. Epub 2021 Oct 6.
This study aimed to identify a novel disease-associated differentially co-expressed mRNA-microRNA (miRNA) that is associated with vasculogenic mimicry (VM) and epithelial-to-mesenchymal transition (EMT) network at different stages of melanoma. By applying weighted gene co-expression network analysis, we constructed a VM+EMT biological network with the available microarray dataset downloaded from a public database. Quantitative real-time PCR, immunohistochemical staining, and CD31-periodic acid solution dual staining were performed to confirm the expression of genes associated with EMT and VM formation in subjects with malignant melanoma (n = 18) and primary melanoma (n = 13) and in healthy subjects (n = 10). Our findings suggested that phosphatidylserine-specific phospholipase A1-alpha (PLA1A) and dermokine (DMKN) genes function as oncogenes that trigger VM and EMT processes during melanomagenesis on interaction with miR-370, miR-563, and miR-770-5p. PLA1A and DMKN genes can be considered potential VM+EMT network-based diagnostic biomarkers for distinguishing between melanoma patients. We postulate that a network with altered PLA1A/miR-563 and DMNK/miR-770-5p/miR-370 may contribute to melanomagenesis by triggering the EMT signaling pathway and VM formation. This study provides a potentially valuable approach for the early diagnosis and prognosis of melanoma progression.
本研究旨在鉴定一种新的疾病相关差异共表达信使核糖核酸-微小核糖核酸（miRNA），其与黑色素瘤不同阶段的血管生成拟态（VM）和上皮-间质转化（EMT）网络相关。通过应用加权基因共表达网络分析，我们利用从公共数据库下载的可用微阵列数据集构建了一个VM+EMT生物网络。对18例恶性黑色素瘤患者、13例原发性黑色素瘤患者和10例健康受试者进行了定量实时聚合酶链反应、免疫组织化学染色及CD31-高碘酸溶液双重染色，以确认与EMT和VM形成相关基因的表达。我们的研究结果表明，磷脂酰丝氨酸特异性磷脂酶A1-α（PLA1A）和皮肤因子（DMKN）基因作为癌基因，在黑色素瘤发生过程中与miR-370、miR-563和miR-770-5p相互作用时触发VM和EMT过程。PLA1A和DMKN基因可被视为基于VM+EMT网络区分黑色素瘤患者的潜在诊断生物标志物。我们推测，PLA1A/miR-563和DMNK/miR-770-5p/miR-370改变的网络可能通过触发EMT信号通路和VM形成促进黑色素瘤发生。本研究为黑色素瘤进展的早期诊断和预后提供了一种潜在有价值的方法。
