دانلود رایگان مقاله SOX2 سرکوب تحرک سرطان اوروتلیال با ارتقا حالت S100A14

Abstract

Sex-determining region Y (SRY)-box protein 2 (SOX2) plays a critical role in stem cell maintenance and carcinogenesis. In addition to its function as a minor-groove DNA binding transcription factor, our previous study showed that SOX2 also acts as a RNA binding protein. In current study, we first showed that SOX2 displayed high affinity toward the mRNA encoding S100A14 in BFTC905 and that depletion of SOX2 resulted in a decrease of S100A14 mRNA and protein level. To characterize the RNA binding sequence recognized by SOX2, oligomer-directed RNase H digestion was coupled to the cross-linking before immunoprecipitation assay to demonstrate that SOX2 preferentially binds to the 3′-UTR of the S100A14 mRNA. Using EGFP-S100A14 3′-UTR reporters and mobility shift assay, we identified that the binding sequence on the 3′-UTR of the S100A14 mRNA exhibits a stem-loop structure. Together, our data indicates that SOX2 enhances S100A14 expression by binding to the 3′-UTR of the S100A14 mRNA. Functionally, depletion of SOX2 increases growth and mobility of BFTC905. Knock-down of S100A14 in BFTC905 also leads to an increase in the number of the cells in the S phase and higher mobility, suggesting that SOX2 suppresses cell growth and mobility through promoting the expression of S100A14. Together, our experimental evidence indicates that SOX2 is capable of exerting its cellular functions by functioning as an RNA binding protein in post-transcriptional regulation.

4. Discussion

In this study, we show that SOX2 binds to the 3′-UTR of the S100A14 mRNA and promotes its expression. Although SOX2 is undoubtedly a transcription factor, our experimental evidence indicates that, in addition to DNA binding, SOX2 also functions as an RNA binding protein. It has been demonstrated that the members of the HMG protein family, including SRY, SOX6, and SOX9, play a role in splicing, thus suggesting that these HMG domain proteins bind to RNA. Our study adds SOX2 to the list of RNAbinding HMG proteins and implies that other HMG proteins function in post-transcriptional regulation as well. It was reported that p53 participates in microRNA biogenesis and that WT1 functions in splicing. Together, these findings raise the possibility that a subset of transcription factors also bind to RNA and participate in post-transcriptional regulation. Post-transcriptional regulation includes alternative splicing, the modulation of mRNA stability, and the control of translation efficiency [31]. Due to the methodology employed in this study, only those genes with their mRNA stability regulated by SOX2 were identified, and we did not rule out that SOX2 may also participate in other post-transcriptional regulation mechanisms.