Alternative splicing variant of NRP/B promotes tumorigenesis of gastric cancer
Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human g...
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Published in | BMB reports Vol. 55; no. 7; pp. 348 - 353 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Korea (South)
Korean Society for Biochemistry and Molecular Biology
31.07.2022
생화학분자생물학회 |
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Abstract | Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer. [BMB Reports 2022; 55(7): 348-353]. |
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AbstractList | Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation
in
vivo
. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer. Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes totumorigenic activity in highly malignant gastric cancer throughdissociation from the tumor repressor, HDAC5. NRP/B mRNAexpression is significantly higher in the human gastric cancertissues than in the normal tissues. Further, high levels of boththe NRP/B splice variant and Lgr5, but not the full-length protein,are found in highly tumorigenic gastric tumor cells, but notin non-tumorigenic cells. The loss of NRP/B markedly inhibitscell migration and invasion, which reduces tumor formation invivo. Importantly, the inhibition of alternative splicing increasesthe levels of NRP/B-1 mRNA and protein in AGS cells. The ectopicexpression of full-length NRP/B exhibits tumor-suppressiveactivity, whereas NRP/B-2 induces the noninvasive human gastriccancer cells tumorigenesis. The splice variant NRP/B-2 whichloses the capacity to interact with tumor repressors promotedoncogenic activity, suggesting that the BTB/POZ domain in theN-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/Bgene is a potential novel target for the treatment of gastrointestinalcancer. KCI Citation Count: 0 Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer. [BMB Reports 2022; 55(7): 348-353]. |
Author | Hahn, Soojung Mok, Bo Ram Yoo, Jongman Kim, Dong Hyun Kim, Aram Kim, Tae-Aug |
AuthorAffiliation | 4 Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea 2 Department of Microbiology, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488, Korea 3 Organoidsciences Ltd., Seongnam 13488, Korea 1 Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488, Korea |
AuthorAffiliation_xml | – name: 3 Organoidsciences Ltd., Seongnam 13488, Korea – name: 4 Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea – name: 1 Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488, Korea – name: 2 Department of Microbiology, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488, Korea |
Author_xml | – sequence: 1 givenname: Aram surname: Kim fullname: Kim, Aram organization: Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea – sequence: 2 givenname: Bo Ram surname: Mok fullname: Mok, Bo Ram organization: Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea – sequence: 3 givenname: Soojung surname: Hahn fullname: Hahn, Soojung organization: Department of Microbiology, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Organoidsciences Ltd., Seongnam 13488, Korea – sequence: 4 givenname: Jongman surname: Yoo fullname: Yoo, Jongman organization: Department of Microbiology, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Organoidsciences Ltd., Seongnam 13488, Korea – sequence: 5 givenname: Dong Hyun surname: Kim fullname: Kim, Dong Hyun organization: Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea – sequence: 6 givenname: Tae-Aug surname: Kim fullname: Kim, Tae-Aug organization: Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea |
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Snippet | Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in... Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes totumorigenic activity in highly... |
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StartPage | 348 |
SubjectTerms | Alternative Splicing - genetics Carcinogenesis - genetics Cell Line, Tumor Gastrointestinal Neoplasms Gene Expression Regulation, Neoplastic Humans RNA, Messenger Stomach Neoplasms - genetics 화학 |
Title | Alternative splicing variant of NRP/B promotes tumorigenesis of gastric cancer |
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