Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer
Abstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SN...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-021-02246-7 |
| _version_ | 1819024251009630208 |
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| author | Liya Liu Youqin Chen Xiaoying Lin Meizhu Wu Jiapeng Li Qiurong Xie Thomas J. Sferra Yuying Han Huixin Liu Liujing Cao Mengying Yao Jun Peng Aling Shen |
| author_facet | Liya Liu Youqin Chen Xiaoying Lin Meizhu Wu Jiapeng Li Qiurong Xie Thomas J. Sferra Yuying Han Huixin Liu Liujing Cao Mengying Yao Jun Peng Aling Shen |
| author_sort | Liya Liu |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. Methods The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. Results SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. Conclusions These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC. |
| first_indexed | 2024-12-21T04:51:49Z |
| format | Article |
| id | doaj.art-404c378368a94af6bf3788c451291208 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-21T04:51:49Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-404c378368a94af6bf3788c4512912082022-12-21T19:15:26ZengBMCCancer Cell International1475-28672021-10-0121111410.1186/s12935-021-02246-7Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancerLiya Liu0Youqin Chen1Xiaoying Lin2Meizhu Wu3Jiapeng Li4Qiurong Xie5Thomas J. Sferra6Yuying Han7Huixin Liu8Liujing Cao9Mengying Yao10Jun Peng11Aling Shen12Academy of Integrative Medicine, Fujian University of Traditional Chinese MedicineDepartment of Pediatrics, Case Western Reserve University School of Medicine, UH Rainbow Babies and Children’s HospitalAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineDepartment of Physical Education, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineDepartment of Pediatrics, Case Western Reserve University School of Medicine, UH Rainbow Babies and Children’s HospitalAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAcademy of Integrative Medicine, Fujian University of Traditional Chinese MedicineAbstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. Methods The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. Results SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. Conclusions These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.https://doi.org/10.1186/s12935-021-02246-7Colorectal cancerSyntrophin beta 1GrowthOverall survivalProtein kinase N2 |
| spellingShingle | Liya Liu Youqin Chen Xiaoying Lin Meizhu Wu Jiapeng Li Qiurong Xie Thomas J. Sferra Yuying Han Huixin Liu Liujing Cao Mengying Yao Jun Peng Aling Shen Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer Cancer Cell International Colorectal cancer Syntrophin beta 1 Growth Overall survival Protein kinase N2 |
| title | Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer |
| title_full | Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer |
| title_fullStr | Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer |
| title_full_unstemmed | Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer |
| title_short | Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer |
| title_sort | upregulation of sntb1 correlates with poor prognosis and promotes cell growth by negative regulating pkn2 in colorectal cancer |
| topic | Colorectal cancer Syntrophin beta 1 Growth Overall survival Protein kinase N2 |
| url | https://doi.org/10.1186/s12935-021-02246-7 |
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