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. 2022 Apr 13:12:802941.
doi: 10.3389/fonc.2022.802941. eCollection 2022.

Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma

Min-Yun Cai  1 , Yue-Li Xu  1 , Hua Rong  2 , Hai Yang  1
Affiliations

Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma

Min-Yun Cai et al. Front Oncol. .

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.

Keywords: MMP; Palmd; Uveal melanoma; ZNF263; metastasis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
DEGs in UM metastasis. (A) Venn diagram of DEGs from GSE22138 and GSE156877. The expression of 5 genes significantly down-regulated in GSE22138 (B) and GSE156877 (C). The expression of 13 genes significantly up-regulated in GSE22138 (D) and GSE156877 (E). *P < 0.05.
Figure 2
Figure 2
UM patients with high expression of PALMD have a better prognosis. The (A) overall survival and (B) disease-free survival of UM patients with low or high PALMD expression. Data from the GEPIA.
Figure 3
Figure 3
Low level of PALMD is beneficial to the motility and metastasis of UM cells. siRNA specifically targeting PALMD or pcDNA3.1 overexpression plasmid was transfected into 92-1 (A) and Mel270 (B) cells to down- (KD) or up- (OV) regulate the expression of PALMD. After transfection, the invasion of 92-1 (C) and Mel270 (D) cells was measured using Transwell assay, the migration of 92-1 (E) and Mel270 (F) cells was detected using scratch assay. *P < 0.05.
Figure 4
Figure 4
PALMD on MMP expression and proliferation of UM cells. After transfection of siRNA specifically targeting PALMD (KD) or pcDNA3.1 overexpression plasmid (OV), the MMP2 and MMP9 expression of 92-1 (A) and Mel270 (B) cells was measured with ELISA, the proliferation of 92-1 (C) and Mel270 (D) cells was detected with CCK-8 assay. *P < 0.05.
Figure 5
Figure 5
ZNF263 is responsible for the transcriptional regulation of PALMD. (A) ZNF263 was predicted to be a transcription factor binding to the PALMD promoter, and the binding site was AATGGGAGGATT. Data from JASPAR databases. (B) Luciferase reporter assay in 92-1 cells. (C) PCR and agarose gel amplification and detection of DNA sequences bound to the ZNF263 protein in 92-1 cells overexpressed ZNF263. (D) The effect of ZNF263 down- or up- regulated expression on PALMD protein expression was detected in 92-1 cells with western blot. *P < 0.05.
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