ZNF667‐AS1, a positively regulating MEGF10, inhibits the progression of uveal melanoma by modulating cellular aggressiveness

Abstract

Zinc finger protein 667‐antisense RNA 1 (ZNF667‐AS1) is a member of the C2H2 zinc finger protein family. However, the exact effect of ZNF667‐AS1 in uveal melanoma (UM) progression has not been elucidated. The biological roles of ZNF667‐AS1 and MEGF10 were assessed using cell counting kit‐8 and flow cytometry. Quantitative reverse‐transcription polymerase chain reaction and Western blot analyses were conducted to measure the expression of subjects. ZNF667‐AS1 expression was significantly decreased in metastasized UM tissues and its low expression was related to poorer prognosis of UM patients. MEGF10 expression was positively associated with ZNF667‐AS1 expression. The inhibitory effect of ZNF667‐AS1 overexpression on UM cellular malignant behaviors could be reversed by MEGF10 knockdown, which was re‐ascertained by the detection of corresponding protein levels (p53, cyclin D1, Bcl‐2, and Bax). In conclusion, ZNF667‐AS1 might play an inhibitory role in the development of UM by regulating cellular aggressiveness, which was partially realized by positively regulating MEGF10.

LncRNA MORT (ZNF667-AS1) in Cancer—Is There a Possible Role in Gynecological Malignancies?

“…It was also reported when comparing colon adenoma and carcinoma cohorts, further confirming that ZNF667-AS1 silencing is likely to occur in the premalignant state [90]. ZNF667-AS1 is known to be frequently silenced in numerous cancers such as melanoma [30], colorectal carcinoma [32], and gastric cancer [91]. In a study characterizing the epigenetic landscape of genes encoding lncRNAs across 6475 tumors and 455 cancer cell lines, ZNF667-AS1 was identified to be a hypermethylated lncRNA in most tumors [92].…”

“…In cancer, ZNF667-AS1 has been implicated in both promoting tumor progression and tumor suppression depending on the cancer type [26][27][28][29][30][31][32][33][34][35][36][37] (Table 1). In laryngeal squamous cell carcinoma (LSCC), decreased ZNF667-AS1 levels were associated with increased migration and invasion together with increased levels of mesenchymal markers and a reduction in epithelial markers.…”

“…The fact that the downregulation of ZNF667-AS1 exhibits an inhibitory effect on the viability, invasion, and migration of esophageal cancer cells suggests that it plays a tumor suppressor role in esophageal cancers [29]. Yang et al investigated the role of ZNF667-AS1 and its potential mechanism with MEGF10 [30], a type I transmembrane protein consisting of 17 EGF-like domains in the extracellular region, which has increased expression in the central nervous system, retina, myoblasts, and muscle satellite cells in tissues derived from uveal melanoma (UM). A reduced expression of ZNF667-AS1 has been shown in UM tissues and its downregulation is correlated with poor prognosis, indicating that ZNF667-AS1 may have an inhibitory role in the development of UM via the regulation of cellular aggressiveness [30].…”

“…Yang et al investigated the role of ZNF667-AS1 and its potential mechanism with MEGF10 [30], a type I transmembrane protein consisting of 17 EGF-like domains in the extracellular region, which has increased expression in the central nervous system, retina, myoblasts, and muscle satellite cells in tissues derived from uveal melanoma (UM). A reduced expression of ZNF667-AS1 has been shown in UM tissues and its downregulation is correlated with poor prognosis, indicating that ZNF667-AS1 may have an inhibitory role in the development of UM via the regulation of cellular aggressiveness [30]. Huang et al investigated the role of ZNF667-AS1 in lung adenocarcinoma (LUAD), where it was shown that ZNF667-AS1 is downregulated, while miRNA-223 is upregulated [31].…”

Do Extracellular RNAs Provide Insight into Uveal Melanoma Biology?

“…In the last few decades, researchers have focused their attention on the role of lncRNAs in carcinogenesis [ 106 ]. Moreover, lncRNAs were found to be involved in the regulation of a plethora of cancer-related processes in UM [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. Given the important contribution of lncRNAs to cancer progression, their potential application as circulating biomarkers has been investigated.…”