Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2

Abstract

Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in many human cancers. Many lncRNAs show aberrant expression in cancer, and some of them play critical roles in tumor proliferation, invasion, and metastasis. However, the regulatory functions of lncRNAs in melanoma progression remain to be elucidated. We utilized the Real-time PCR methodology to determine the expression of LINC-PINT in melanoma cell lines. To evaluate the effect of LINC-PINT on tumorigenesis of melanoma, we used Cell Counting Kit-8 (CCK8) and colony formation assay. Flow cytometry assay was used to detect the function of LINC-PINT on cell cycle status. PINT-interacting proteins were identified by chromatin isolation using RNA purification (ChIRP). Microarray assay and bioinformatics analysis were used to find the potential target genes of LINC-PINT and the status of LINC-PINT target gene candidate was verified using chromatin immunoprecipitation assay (ChIP). LINC-PINT plays a role in suppressing the tumorigenicity of melanoma, which was further determined by xenograft model assay. LINC-PINT was significantly downregulated in melanoma tissues and cell lines. The overexpression of LINC-PINT in tumor cells resulted in significant tumor growth reduction and migration inhibition in A375, Mum2B and CRMM1 cells. Results based on the in vivo xenograft model were further consistent with the in vitro findings that LINC-PINT impeded growth and metastasis of melanoma cells. Microarray assay and bioinformatics analysis indicated that CDK1, CCNA2, AURKA, and PCNA were potential targets of LINC-PINT. In conclusion, LINC-PINT inhibits the tumorigenicity of melanoma through recruiting EZH2 to the promoter of its target genes, leading to H3K27 trimethylation and epigenetic silencing of target genes. LINC-PINT may serve as a novel diagnostic and therapeutic target for melanoma.

RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

“…Recent evidence indicates that EZH2 plays a vital RNA binding role, contributing to the regulation of various lncRNAs. Xu et al reported that lncRNA LINC-PINT inhibits melanoma cell proliferation and migration [38]. LncRNA LINC-PINT could recruit EZH2 to the promoters of its target genes (CDK1, CCNA2, AURKA and PCNA), resulting in H3K27 trimethylation and gene silencing [38].…”

“…Xu et al reported that lncRNA LINC-PINT inhibits melanoma cell proliferation and migration [38]. LncRNA LINC-PINT could recruit EZH2 to the promoters of its target genes (CDK1, CCNA2, AURKA and PCNA), resulting in H3K27 trimethylation and gene silencing [38]. Liu et al found that linc01088 promotes cell proliferation via binding to EZH2 and inhibits P21 expression in non-small cell lung cancer [39].…”

Long Noncoding RNA LINC-PINT Suppresses Cell Proliferation, Invasion, and EMT by Blocking Wnt/β-Catenin Signaling in Glioblastoma

“… Zhang et al (2019) showed that LINC-PINT acted as a tumor suppressor by sponging miR-543 and miR-576–5p in esophageal cancer. Xu et al (2019c) verified that LINC-PINT suppresses cell proliferation and migration of melanoma via recruiting EZH2. Interestingly, in clear cell renal cell carcinoma, LINC-PINT could also exert an oncogenic role.…”

“…Long intergenic non-protein coding RNA p53 induced transcript, LINC-PINT, which localizes at the human chromosome 7q32.3, has been demonstrated to act as a tumor suppressor in various kinds of cancers such as colorectal adenocarcinoma, gastric carcinoma, non-small cell lung cancer, esophageal cancer, and melanoma ( Marín-Béjar et al, 2017 ; Feng et al, 2019 ; Xu et al, 2019c ; Zhang et al, 2019 ). Moreover, LINC-PINT could also exert an oncogene role in clear cell renal cell carcinoma ( Duan et al, 2019 ).…”

Inhibition of miR-490-5p Promotes Human Adipose-Derived Stem Cells Chondrogenesis and Protects Chondrocytes via the PITPNM1/PI3K/AKT Axis

“…The effect of knockdown or overexpression of miRNA on the proliferation of PHCs was studied using the Cell Counting Kit-8 (CCK-8; Sigma-Aldrich, United States) as described previously (Xu et al, 2019).…”