The Effect of hnRNPK/Beclin1 Signaling on the Drug Resistance of Imatinib in Ph+ Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of hnRNPK/Beclin1 signaling on the drug resistance of imatinib in Ph+ leukemia.@*METHODS@#Expression level of hnRNPK was verified in the imatinib resistant and sensitive Ph+ leukemia cell lines by using Western blot. hnRNPK expression was down-regulated by using RNAi. Expression level of LC3I/II and Beclin1 were detected by Western blot and the sensitivity of imatinib was analyzed by CCK-8 assay before and after modulation of hnRNPK expression.@*RESULTS@#hnRNPK showed overexpressed in imatinib resistant leukemia cell line. After the expression level of hnRNPK was down-regulated by RNAi, the sensitivity of drug resistance lines to imatinib restored, while the expression level of LC3I/II and Beclin1 were consistant with the modulation of hnRNPK expression.@*CONCLUSION@#hnRNP K/Beclin1 signaling may be involved in the development of imatinib resistance in Ph+ leukemia through the regulation of autophagy.

Recent progress in research of heterogeneous nuclear ribonucleoprotein K related with tumor pathogenesis and progression / 中国比较医学杂志

Over the past few decades, the classification of oncogenes or tumor suppressor genes has been an important topic in cancer biology. However,it is difficult to classify some genes. Heterogeneous nuclear ribonucleoprotein K(HNRNPK)is a nucleic acid-binding protein,which is involved in the regulation of gene expression,signal transduction and many other cellular processes. In recent years, it has been found that HNRNPK is overexpressed in many types of tumors,and its overexpression is negatively correlated with the prognosis of patients,suggesting that HNRNPK may play a role as an oncogene in tumorigenesis. In contrast,however,HNRNPK has also been considered as a tumor suppressor gene in acute myeloid leukemia(AML). Therefore, in this article we summarize and discuss the recent progress in the molecular functions and regulatory mechanisms of HNRNPK in tumorigenesis and progression.

ERK1/2-mediated Cytoplasmic Accumulation of hnRNPK Antagonizes TRAIL-induced Apoptosis through Upregulation of XIAP in H1299 Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.</p><p><b>METHODS</b>Nuclear and cytoplasmic protein extraction and immuno？uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.</p><p><b>RESULTS</b>Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.</p><p><b>CONCLUSION</b>Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.</p>