SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop
Abstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal canc...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-02162-8 |
| _version_ | 1819198596739760128 |
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| author | Zehua Bian Mingyue Zhou Kaisa Cui Fan Yang Yulin Cao Shengbai Sun Bingxin Liu Liang Gong Jiuming Li Xue Wang Chaoqun Li Surui Yao Yuan Yin Shenglin Huang Bojian Fei Zhaohui Huang |
| author_facet | Zehua Bian Mingyue Zhou Kaisa Cui Fan Yang Yulin Cao Shengbai Sun Bingxin Liu Liang Gong Jiuming Li Xue Wang Chaoqun Li Surui Yao Yuan Yin Shenglin Huang Bojian Fei Zhaohui Huang |
| author_sort | Zehua Bian |
| collection | DOAJ |
| description | Abstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy. |
| first_indexed | 2024-12-23T03:02:58Z |
| format | Article |
| id | doaj.art-1e6f84728b4e4065a415298aff24a600 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-23T03:02:58Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-1e6f84728b4e4065a415298aff24a6002022-12-21T18:02:22ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-11-0140111410.1186/s13046-021-02162-8SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loopZehua Bian0Mingyue Zhou1Kaisa Cui2Fan Yang3Yulin Cao4Shengbai Sun5Bingxin Liu6Liang Gong7Jiuming Li8Xue Wang9Chaoqun Li10Surui Yao11Yuan Yin12Shenglin Huang13Bojian Fei14Zhaohui Huang15Wuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan UniversityDepartment of Surgical Oncology, Affiliated Hospital of Jiangnan UniversityWuxi Cancer Institute, Affiliated Hospital of Jiangnan UniversityAbstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.https://doi.org/10.1186/s13046-021-02162-8CRClncRNASNHG17PES1FOSL2miR-339-5p |
| spellingShingle | Zehua Bian Mingyue Zhou Kaisa Cui Fan Yang Yulin Cao Shengbai Sun Bingxin Liu Liang Gong Jiuming Li Xue Wang Chaoqun Li Surui Yao Yuan Yin Shenglin Huang Bojian Fei Zhaohui Huang SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop Journal of Experimental & Clinical Cancer Research CRC lncRNA SNHG17 PES1 FOSL2 miR-339-5p |
| title | SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop |
| title_full | SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop |
| title_fullStr | SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop |
| title_full_unstemmed | SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop |
| title_short | SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop |
| title_sort | snhg17 promotes colorectal tumorigenesis and metastasis via regulating trim23 pes1 axis and mir 339 5p fosl2 snhg17 positive feedback loop |
| topic | CRC lncRNA SNHG17 PES1 FOSL2 miR-339-5p |
| url | https://doi.org/10.1186/s13046-021-02162-8 |
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