Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth

Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s...

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Veröffentlicht in:Cancers 2021-02, Vol.13 (5), p.980
Hauptverfasser: Chan, Loucia Kit Ying, Lau, Tat San, Chung, Kit Ying, Tam, Chit, Cheung, Tak Hong, Yim, So Fan, Lee, Jacqueline Ho Sze, Leung, Ricky Wai Tak, Qin, Jing, Or, Yvonne Yan Yan, Lo, Kwok Wai, Kwong, Joseph
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container_end_page
container_issue 5
container_start_page 980
container_title Cancers
container_volume 13
creator Chan, Loucia Kit Ying
Lau, Tat San
Chung, Kit Ying
Tam, Chit
Cheung, Tak Hong
Yim, So Fan
Lee, Jacqueline Ho Sze
Leung, Ricky Wai Tak
Qin, Jing
Or, Yvonne Yan Yan
Lo, Kwok Wai
Kwong, Joseph
description Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/β, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.
doi_str_mv 10.3390/cancers13050980
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Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/β, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13050980</identifier><identifier>PMID: 33652749</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acetylation ; AKT1 protein ; Bisulfite ; Breast cancer ; Cell culture ; Chromatin ; Cytokines ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA probes ; Endometrial cancer ; Endometrium ; Epigenetics ; Epithelial cells ; Extracellular signal-regulated kinase ; Gene expression ; Gene regulation ; Genital cancers ; Histones ; Hybridization ; Hypersensitivity ; Immunoprecipitation ; Inflammation ; Interleukin 7 ; Isoforms ; Lungs ; Metastasis ; Ovarian cancer ; Polymerase chain reaction ; Proteins ; Proteomes ; Skin ; Thymus ; Transcription ; Transcriptomes ; Tumor cell lines ; Tumors ; Vagina</subject><ispartof>Cancers, 2021-02, Vol.13 (5), p.980</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth</title><author>Chan, Loucia Kit Ying ; Lau, Tat San ; Chung, Kit Ying ; Tam, Chit ; Cheung, Tak Hong ; Yim, So Fan ; Lee, Jacqueline Ho Sze ; Leung, Ricky Wai Tak ; Qin, Jing ; Or, Yvonne Yan Yan ; Lo, Kwok Wai ; Kwong, Joseph</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-7648509e62d1f3bf37e7dbcb3c6e70912daa8c66b72af81d6b2069a27f7eb8a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetylation</topic><topic>AKT1 protein</topic><topic>Bisulfite</topic><topic>Breast cancer</topic><topic>Cell culture</topic><topic>Chromatin</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA probes</topic><topic>Endometrial 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Growth</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-02-26</date><risdate>2021</risdate><volume>13</volume><issue>5</issue><spage>980</spage><pages>980-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/β, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33652749</pmid><doi>10.3390/cancers13050980</doi><orcidid>https://orcid.org/0000-0002-3380-6882</orcidid><orcidid>https://orcid.org/0000-0002-3175-1144</orcidid><orcidid>https://orcid.org/0000-0002-3488-6124</orcidid><orcidid>https://orcid.org/0000-0003-2315-9690</orcidid><oa>free_for_read</oa></addata></record>
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source MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central; EZB Electronic Journals Library; PubMed Central Open Access
subjects Acetylation
AKT1 protein
Bisulfite
Breast cancer
Cell culture
Chromatin
Cytokines
Deoxyribonucleic acid
DNA
DNA methylation
DNA probes
Endometrial cancer
Endometrium
Epigenetics
Epithelial cells
Extracellular signal-regulated kinase
Gene expression
Gene regulation
Genital cancers
Histones
Hybridization
Hypersensitivity
Immunoprecipitation
Inflammation
Interleukin 7
Isoforms
Lungs
Metastasis
Ovarian cancer
Polymerase chain reaction
Proteins
Proteomes
Skin
Thymus
Transcription
Transcriptomes
Tumor cell lines
Tumors
Vagina
title Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth
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