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KMID : 0624620220550070348
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BMB Reports
2022 Volume.55 No. 7 p.348 ~ p.353
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Alternative splicing variant of NRP/B promotes tumorigenesis of gastric cancer
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Kim A-Ram
Mok Bo-Ram
Hahn Soo-Jung
Yoo Jong-Man
Kim Dong-Hyun
Kim Tae-Aug
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Abstract
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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.
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KEYWORD
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Alternative splicing, Gastric cancer, HDAC5, Lgr5, NRP/B
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