ABSTRACT
Uveal melanoma (UM) is a highly aggressive disease. There is an urgent need to develop the metastasis prediction markers of UM. This study aims to detect the key role of PALMD in UM metastasis. Transcriptome sequencing results of 2 sets of UM metastatic samples (GSE22138 and GSE156877) were downloaded from the Gene Expression Omnibus (GEO), and 18 overlapping differentially expressed genes were screened out, including PALMD. PALMD was significantly underexpressed in metastatic UM tissue. Low expression of PALMD was associated with poor prognosis in UM patients. The decreased expression of PALMD promoted the invasion and migration of 92-1 and Mel270 cells, while the high expression of PALMD inhibited the invasion and migration of UM cells. Furthermore, the levels of matrix metallopeptidase (MMP) 2 and MMP9 increased after transfection of siRNAs specifically targeting PALMD, whereas the levels of MMP2 and MMP9 were decreased after PALMD overexpression. However, PALMD did not affect the proliferation of UM cells. In addition, ZNF263 promoted the transcription of PALMD through the putative binding sequence using the JASPAR database, luciferase reporter gene analysis and chromatin immunoprecipitation assay. In summary, the expression of PALMD regulated by ZNF263 plays an important role in UM metastasis.
ABSTRACT
Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) is a member of the C2 H2 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.
