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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| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/5/980 |
| _version_ | 1797395167559286784 |
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| author | Loucia Kit Ying Chan Tat San Lau Kit Ying Chung Chit Tam Tak Hong Cheung So Fan Yim Jacqueline Ho Sze Lee Ricky Wai Tak Leung Jing Qin Yvonne Yan Yan Or Kwok Wai Lo Joseph Kwong |
| author_facet | Loucia Kit Ying Chan Tat San Lau Kit Ying Chung Chit Tam Tak Hong Cheung So Fan Yim Jacqueline Ho Sze Lee Ricky Wai Tak Leung Jing Qin Yvonne Yan Yan Or Kwok Wai Lo Joseph Kwong |
| author_sort | Loucia Kit Ying Chan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:30:33Z |
| format | Article |
| id | doaj.art-8444f3cf176d46d88e312fefa5c7b043 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:30:33Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8444f3cf176d46d88e312fefa5c7b0432023-12-11T18:34:30ZengMDPI AGCancers2072-66942021-02-0113598010.3390/cancers13050980Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour GrowthLoucia Kit Ying Chan0Tat San Lau1Kit Ying Chung2Chit Tam3Tak Hong Cheung4So Fan Yim5Jacqueline Ho Sze Lee6Ricky Wai Tak Leung7Jing Qin8Yvonne Yan Yan Or9Kwok Wai Lo10Joseph Kwong11Department of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 510006, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen 510006, ChinaDepartment of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Obstetrics of Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaThymic 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.https://www.mdpi.com/2072-6694/13/5/980TSLPshort isoformovarian cancerendometrial cancerepigenetic regulationtumour promotion |
| spellingShingle | Loucia Kit Ying Chan Tat San Lau Kit Ying Chung Chit Tam Tak Hong Cheung So Fan Yim Jacqueline Ho Sze Lee Ricky Wai Tak Leung Jing Qin Yvonne Yan Yan Or Kwok Wai Lo Joseph Kwong Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth Cancers TSLP short isoform ovarian cancer endometrial cancer epigenetic regulation tumour promotion |
| title | Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth |
| title_full | Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth |
| title_fullStr | Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth |
| title_full_unstemmed | Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth |
| title_short | Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth |
| title_sort | short form thymic stromal lymphopoietin sftslp is the predominant isoform expressed by gynaecologic cancers and promotes tumour growth |
| topic | TSLP short isoform ovarian cancer endometrial cancer epigenetic regulation tumour promotion |
| url | https://www.mdpi.com/2072-6694/13/5/980 |
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