Alternative splicing variant of NRP/B promotes tumorigenesis of gastric cancer

• Published in: BMB reports Vol. 55; no. 7; pp. 348 - 353
• Main Authors: Kim, Aram, Mok, Bo Ram, Hahn, Soojung, Yoo, Jongman, Kim, Dong Hyun, Kim, Tae-Aug
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 31.07.2022; 생화학분자생물학회
• Subjects: Alternative Splicing - genetics; Carcinogenesis - genetics; Cell Line, Tumor; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; RNA, Messenger; Stomach Neoplasms - genetics; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2022.55.7.034

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].