Universität zu Köln

Xu, Yangfan, Wang, Huixue, Li, Fang, Heindl, Ludwig M., He, Xiaoyu, Yu, Jie, Yang, Jie, Ge, Shengfang, Ruan, Jing, Jia, Renbing and Fan, Xianqun (2019). Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2. Front. Cell. Dev. Biol., 7. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2296-634X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Xu, Yangfan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Huixue UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Fang UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindl, Ludwig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED He, Xiaoyu UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Jie UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Jie UNSPECIFIED UNSPECIFIED UNSPECIFIED Ge, Shengfang UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruan, Jing UNSPECIFIED UNSPECIFIED UNSPECIFIED Jia, Renbing UNSPECIFIED UNSPECIFIED UNSPECIFIED Fan, Xianqun UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124107
DOI:	10.3389/fcell.2019.00350
Journal or Publication Title:	Front. Cell. Dev. Biol.
Volume:	7
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2296-634X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER; METASTASIS; COMPLEXES; INVASION Multiple languages Cell Biology; Developmental Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12410