DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bd-2 inhibitors

Objective:Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer(NSCLC),but no direct Mcl-1 inhibitor is currently available for clinical use.Thus,novel therapeutic strategies are urgently needed to target Mcl-1 and sensitize the anti-NSCLC activity of Bcl-2 inhibitors.Methods:Cell proliferation was measured using sulforhodamine B and colony formation assays,and apoptosis was detected with Annexin V-FITC staining.Gene expression was manipulated using siRNAs and plasmids.Real-time PCR and Western blot were used to measure mRNA and protein levels.Immunoprecipitation and immunofluorescence were used to analyze co-localization o f dual specificity tyrosine-phosphorylation-regulated kinase 1A(DYRK1A)and Mcl-1.Results:Suppression of DYRK1A resulted in reduced Mcl-1 expression in NSCLC cells,whereas overexpression of DYRK1A significantly increased Mcl-1 expression.Suppression of DYRK1A did not alter Mcl-1 mRNA levels,but did result in an accelerated degradation o f Mcl-1 protein in NSCLC cells.Furthermore,DYRK1A mediated proteasome-dependent degradation o f Mcl-1 in NSCLC cells,and DYRK1A co-localized with Mcl-1 in NSCLC cells and was co-expressed with Mcl-1 in tumor samples from lung cancer patients,suggesting that Mcl-1 may be a novel DYRK1A substrate.We showed that combined therapy with harmine and Bcl-2 antagonists significantly inhibited cell proliferation and induced apoptosis in NSCLC cell lines as well as primary NSCLC cells.Conclusions:Mcl-1 is a novel DYRK1A substrate,and the role of DYRK1A in promoting Mcl-1 stability makes it an attractive target for decreasing Bcl-2 inhibitor resistance.

Erratum to DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors

In the published paper1,errors appeared in Figure 1D on page 391.In Figure 1D,an incorrect gel image was shown for Bcl-xL in NCI-H1299 cells.Figure 1D has been updated to correct the mistake above.The errors do not affect the conclusions of this article.We apologize for the errors and for any confusion that they may have caused.

The Preparation and Properties of Starch Based Shape Memory Hydrogel

In this work,the–catechol and–thiol modified starch was prepared by the esterification and amino condensation reaction,then a fully starch based hydrogel was prepared via the thiol-catechol Michael addition reaction.The starch hydrogel gained shape memory behaviors by coordinate with Fe^(3+)ions at alkaline condition.1H-NMR had been used to character the structure of the starch derivatives and its character peaks.The hydrogel’s modulus had also been measured before and after coordinating with Fe^(3+)ions in linear area and the result showed that both the hydrogel’s storage modulus and loss modulus kept constant in linear area from 0.1 rad/s to 100 rad/s,which demonstrated a good network was formed inside the hydrogel.Furthermore,the shape memory behaviors had been tested by changing the pH value in solution.The result showed that the hydrogel can keep its temporary shape in high pH condition and recover to its original state after the shaped hydrogel immersed into acidic solution.This hydrogel might have great application prospects in the field of biomedical and engineering.