Requirement of splicing factor hnRNP A2B1 of hnRNPs for tumorigenesis of melanoma stem cells [post]

Mengqi Chu, Haitao Wan, Xiaobo Zhang
2020 unpublished
Background: Cancer stem cells play essential roles in tumorigenesis, thus being the important targets for tumor therapy. The hnRNP family proteins, the important splicing factors, are found to be associated with tumor progression. However, the influence of hnRNPs on cancer stem cells has not been extensively explored.Methods: Quantitative real-time PCR and Western blot were used to examine the gene expression level. RNA immunoprecipitation assay and RNA sequencing were conducted to identify the
more » ... RNAs interacted with hnRNP A2B1 on a genome-wide scale. The in vivo assays were performed in nude mice.Results: In this study, the results showed that hnRNP A2B1 of 19 hnRNPs was significantly upregulated in melanoma stem cells compared with non-stem cells, suggesting the important role of hnRNP A2B1 in cancer stem cells. The hnRNP A2B1 silencing triggered the cell cycle arrest in G2 phase, leading to apoptosis of melanoma stem cells. The results revealed that hnRNP A2B1 could bind to the precursor mRNAs of pro-apoptosis genes (DAPK1, SYT7 and RNF128) and anti-apoptosis genes (EIF3H, TPPP3 and DOCK2) to regulate the splicing of these 6 genes, thus promoting the expressions of anti-apoptosis genes and suppressing the expressions of pro-apoptosis genes. The in vivo data indicated that hnRNP A2B1 was required for tumorigenesis of melanoma stem cells in vivo by affecting the splicing of TPPP3, DOCK2, EIF3H, RNF128, DAPK1 and SYT7, thus suppressing apoptosis of melanoma stem cells.Conclusions: HnRNP A2B1 was required for tumorigenesis of melanoma stem cells. Therefore our findings presented novel molecular insights into the roles of hnRNPs in cancer stem cells.
doi:10.21203/rs.3.rs-92870/v1 fatcat:utcsptaxwzh4ppzo5nigpfe3me