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 |
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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”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-7648509e62d1f3bf37e7dbcb3c6e70912daa8c66b72af81d6b2069a27f7eb8a23</citedby><cites>FETCH-LOGICAL-c421t-7648509e62d1f3bf37e7dbcb3c6e70912daa8c66b72af81d6b2069a27f7eb8a23</cites><orcidid>0000-0002-3380-6882 ; 0000-0002-3175-1144 ; 0000-0002-3488-6124 ; 0000-0003-2315-9690</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956741/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956741/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33652749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Loucia Kit Ying</creatorcontrib><creatorcontrib>Lau, Tat San</creatorcontrib><creatorcontrib>Chung, Kit Ying</creatorcontrib><creatorcontrib>Tam, Chit</creatorcontrib><creatorcontrib>Cheung, Tak Hong</creatorcontrib><creatorcontrib>Yim, So Fan</creatorcontrib><creatorcontrib>Lee, Jacqueline Ho Sze</creatorcontrib><creatorcontrib>Leung, Ricky Wai Tak</creatorcontrib><creatorcontrib>Qin, Jing</creatorcontrib><creatorcontrib>Or, Yvonne Yan Yan</creatorcontrib><creatorcontrib>Lo, Kwok Wai</creatorcontrib><creatorcontrib>Kwong, Joseph</creatorcontrib><title>Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><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.</description><subject>Acetylation</subject><subject>AKT1 protein</subject><subject>Bisulfite</subject><subject>Breast cancer</subject><subject>Cell culture</subject><subject>Chromatin</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA probes</subject><subject>Endometrial cancer</subject><subject>Endometrium</subject><subject>Epigenetics</subject><subject>Epithelial cells</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genital cancers</subject><subject>Histones</subject><subject>Hybridization</subject><subject>Hypersensitivity</subject><subject>Immunoprecipitation</subject><subject>Inflammation</subject><subject>Interleukin 7</subject><subject>Isoforms</subject><subject>Lungs</subject><subject>Metastasis</subject><subject>Ovarian cancer</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Proteomes</subject><subject>Skin</subject><subject>Thymus</subject><subject>Transcription</subject><subject>Transcriptomes</subject><subject>Tumor cell 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Loucia Kit Ying</creator><creator>Lau, Tat San</creator><creator>Chung, Kit Ying</creator><creator>Tam, Chit</creator><creator>Cheung, Tak Hong</creator><creator>Yim, So Fan</creator><creator>Lee, Jacqueline Ho Sze</creator><creator>Leung, Ricky Wai Tak</creator><creator>Qin, Jing</creator><creator>Or, Yvonne Yan Yan</creator><creator>Lo, Kwok Wai</creator><creator>Kwong, Joseph</creator><general>MDPI 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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 cancer</topic><topic>Endometrium</topic><topic>Epigenetics</topic><topic>Epithelial cells</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genital cancers</topic><topic>Histones</topic><topic>Hybridization</topic><topic>Hypersensitivity</topic><topic>Immunoprecipitation</topic><topic>Inflammation</topic><topic>Interleukin 7</topic><topic>Isoforms</topic><topic>Lungs</topic><topic>Metastasis</topic><topic>Ovarian cancer</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Proteomes</topic><topic>Skin</topic><topic>Thymus</topic><topic>Transcription</topic><topic>Transcriptomes</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Vagina</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chan, Loucia Kit Ying</creatorcontrib><creatorcontrib>Lau, Tat San</creatorcontrib><creatorcontrib>Chung, Kit Ying</creatorcontrib><creatorcontrib>Tam, Chit</creatorcontrib><creatorcontrib>Cheung, Tak Hong</creatorcontrib><creatorcontrib>Yim, So Fan</creatorcontrib><creatorcontrib>Lee, Jacqueline Ho Sze</creatorcontrib><creatorcontrib>Leung, Ricky Wai Tak</creatorcontrib><creatorcontrib>Qin, Jing</creatorcontrib><creatorcontrib>Or, Yvonne Yan Yan</creatorcontrib><creatorcontrib>Lo, Kwok Wai</creatorcontrib><creatorcontrib>Kwong, Joseph</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni 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USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chan, Loucia Kit Ying</au><au>Lau, Tat San</au><au>Chung, Kit Ying</au><au>Tam, Chit</au><au>Cheung, Tak Hong</au><au>Yim, So Fan</au><au>Lee, Jacqueline Ho Sze</au><au>Leung, Ricky Wai Tak</au><au>Qin, Jing</au><au>Or, Yvonne Yan Yan</au><au>Lo, Kwok Wai</au><au>Kwong, Joseph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour 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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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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