Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK/ERK signaling pathway. (1st December 2020)

• Record Type: Journal Article
• Authors: Meng, Ling-Dong; Shi, Guo-Dong; Ge, Wan-Li; Huang, Xu-Min; Chen, Qun; Yuan, Hao; Wu, Peng-Fei; Lu, Yi-Chao; Shen, Peng; Zhang, Yi-Han; Cao, Shou-Ji; Miao, Yi; Tu, Min; Jiang, Kui-Rong
• Is Part Of: Cancer letters. Volume 494(2020)
• Page Start: 107
• Page End: 120
• Publication Date: 2020-12-01
• Subjects: Long noncoding RNAs -- PC -- Ubiquitination -- Invasion -- Splicing; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.08.001
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Pancreatic cancer (PC) is a malignant cancer with high mortality and poor prognosis. In this study, we found that Linc01232 was significantly upregulated in PC tissues and cells and higher Linc01232 expression was associated with poorer prognosis. Linc01232 overexpression promoted and Linc01232 knockdown inhibited the migration and invasion of PC cells. The results of RNA pull-down, RNA Binding Protein Immunoprecipitation (RIP) assays revealed that Linc01232 physically interacted with Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2B1) (680–890 nt fragment with the RNA recognition motif 2 domain) to inhibit its ubiquitin-mediated degradation in PC cells. RNA sequencing was performed to obtain the transcriptional profiles regulated by Linc01232 and we further demonstrated that Linc01232 participated in the alternative splicing of A-Raf by stabilizing HNRNPA2B1 and subsequently regulated the MAPK/ERK signaling pathway. Collected, our study showed that Linc01232/HNRNPA2B1/A-Raf/MAPK axis participated in the progression of PC and provided a potential therapeutic target for PC. Highlights: Linc01232 is significantly upregulated in PC tissues and cells and higher Linc01232 expression is associated with worse prognosis. Linc01232 physically interacts with HNRNPA2B1 (680–890 nt fragment with the RRM2 domain) to inhibit its ubiquitin-mediated degradation in PC cells. Linc01232 promotes PC cell metastasis by participating in the alternative splicing of A-Raf and subsequently regulated the MAPK/ERK signaling pathway.