Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells.
BACKGROUND
Cancer stem cells play essential roles in tumorigenesis, thus forming an important target for tumor therapy. The hnRNP family proteins are important splicing factors that have been 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 gene expressions. RNA immunoprecipitation assays were conducted to identify the RNAs interacted with hnRNP A2B1. The in vivo assays were performed in nude mice.


RESULTS
In this study, the results showed that out of 19 evaluated hnRNPs, hnRNP A2B1 was significantly upregulated in melanoma stem cells compared with non-stem cells, suggesting an important role of hnRNP A2B1 in cancer stem cells. Silencing of hnRNP A2B1 triggered cell cycle arrest in G2 phase, leading to apoptosis of melanoma stem cells. The results also 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 by affecting the splicing of TPPP3, DOCK2, EIF3H, RNF128, DAPK1, and SYT7, thus suppressing apoptosis of melanoma stem cells.


CONCLUSION
Our findings showed the requirement of hnRNP A2B1 for tumorigenesis, thus presenting novel molecular insights into the role of hnRNPs in cancer stem cells.
['Chu|Mengqi|M|', 'Wan|Haitao|H|', 'Zhang|Xiaobo|X|']
D000818:Animals D002471:Cell Transformation, Neoplastic D020690:GTPase-Activating Proteins D020662:Guanine Nucleotide Exchange Factors D034441:Heterogeneous-Nuclear Ribonucleoproteins D008545:Melanoma D051379:Mice D008819:Mice, Nude D014411:Neoplastic Stem Cells D000072260:RNA Splicing Factors
hnRNP Tumorigenesis Melanoma Cancer stem cells Apoptosis