The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.
A universal metal-molecule-metal sandwich architecture by the self-assembly of Ag nanoparticles (NPs) and Au NPs of various shapes interconnected with 4-aminothiophenol (4-ATP) molecules was presented. These Ag NPs/4-ATP/Au NPs sandwich structures were characterized by surface enhanced Raman scattering (SERS) using an off-surface plasmon resonance condition. Enhancement factors (EF) on the order of 10 8 for 9b(b 2 ) vibration mode were observed for the 4-ATP self-assembled monolayers (SAMs) in such sandwich structures. The factors are 2 orders of magnitude larger than that on the monolayer of Au NPs of various shapes under similar condition. More importantly, remarkable increase in the intensity of b 2 vibrational modes, which is characteristic of the charge transfer (CT) behavior between metal NPs and 4-ATP molecules, was observed in these sandwich structures under 1064 nm excitation. The obtained EF on these sandwich structure for 9b(b 2 ) is larger than that for 7a vibration mode by a factor of ∼10 2 , demonstrating the importance of the contribution of the CT mechanism and the CT behavior of metal contacts, which play a significant role in metal-molecule-metal nanosystems. Moreover, enhancement factors depend on the shape of the Au NPs and vary by a factor of 8.
An effective and facile approach for the preparation of multilayered nanostructure of gold nanorods (Au NRs) has been demonstrated. Linear polyethylenimine (LPEI) was selected as a polymeric adhesive layer, and an anionic polyelectrolyte poly(sodium styrenesulfonate) (PSS) was used as the linker of the positively charged Au NRs in multilayered nanostructure. They were deposited onto the LPEI-modified indium-doped tin oxide (ITO) substrate alternately using the layer-by-layer assembly technique via electrostatic interactions. The plasmonic property of the multilayered nanostructure of Au NRs is tunable by the controlled self-assembly process. FE-SEM was used to study the morphologies of the resulted substrates with Au NRs monolayer membrane and with Au NRs multilayered membrane. More importantly, it was found that the multilayered NRs films could be used as a surface-enhanced Raman spectroscopy (SERS) substrate for probing 4-aminothiophenol (4-ATP).
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