Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway
Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differe...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661823002967 |
| _version_ | 1827728452875190272 |
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| author | Mingyue Tan Qi Pan Hua Gong Xinyu Zhai Zhong Wan Minyao Ge Jianyi Gu Dingguo Zhang Xia Chen Dongliang Xu |
| author_facet | Mingyue Tan Qi Pan Hua Gong Xinyu Zhai Zhong Wan Minyao Ge Jianyi Gu Dingguo Zhang Xia Chen Dongliang Xu |
| author_sort | Mingyue Tan |
| collection | DOAJ |
| description | Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells. |
| first_indexed | 2024-03-10T23:29:21Z |
| format | Article |
| id | doaj.art-0e19bd7393a44289b9caa2496840d6ac |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-10T23:29:21Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-0e19bd7393a44289b9caa2496840d6ac2023-11-19T04:34:14ZengElsevierPharmacological Research1096-11862023-11-01197106940Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathwayMingyue Tan0Qi Pan1Hua Gong2Xinyu Zhai3Zhong Wan4Minyao Ge5Jianyi Gu6Dingguo Zhang7Xia Chen8Dongliang Xu9Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Urology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, ChinaDepartment of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDepartment of Urology, Shanghai Pudong New Area People's Hospital, Shanghai 201299, China; Correspondence to: Department of Urology, Shanghai Pudong New Area People's Hospital, No.490 Chuanhuan South Road, Chuansha Town, Pudong New Area, Shanghai 201299, China.Department of Endocrinology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China; Correspondence to: Department of Endocrinology, Gongli Hospital of Shanghai Pudong New Area, No.219 Miaopu Road, Pudong New Area, Shanghai 200135, China.Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Correspondence to: Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No.528 Zhangheng Road, Pudong New Area, Shanghai 201203, China.Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells.http://www.sciencedirect.com/science/article/pii/S1043661823002967Super-enhancerSNHG15FOSL1WNTBladder cancer |
| spellingShingle | Mingyue Tan Qi Pan Hua Gong Xinyu Zhai Zhong Wan Minyao Ge Jianyi Gu Dingguo Zhang Xia Chen Dongliang Xu Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway Pharmacological Research Super-enhancer SNHG15 FOSL1 WNT Bladder cancer |
| title | Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway |
| title_full | Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway |
| title_fullStr | Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway |
| title_full_unstemmed | Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway |
| title_short | Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway |
| title_sort | super enhancer associated snhg15 cooperating with fosl1 contributes to bladder cancer progression through the wnt pathway |
| topic | Super-enhancer SNHG15 FOSL1 WNT Bladder cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1043661823002967 |
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