OBJECTIVE: To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). METHODS: Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children's Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome", "Au-Kline syndrome", "HNRNPK" and "AKS". The research period was set as from January 1, 2000 to December 31, 2020. RESULTS: The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c.478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. CONCLUSION The AKS in this child may be attributed to the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Humans ; Male ; Abnormalities, Multiple/genetics* ; Genetic Testing ; Heterogeneous-Nuclear Ribonucleoprotein K/genetics* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Infant, Newborn

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.
Mice ; Animals ; Cementogenesis ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; RNA, Long Noncoding/genetics* ; Parathyroid Hormone ; Receptors, G-Protein-Coupled/metabolism*

Enterovirus 71 (EV71) is a neurotropic pathogen that can induce hand, foot and mouth disease in children. There is an appreciable mortality rate after EV71 infections. The mechanism of action of EV71 replication is not known. Recent work has identified some of cell factors of the host that participate in the synthesis of the RNA and proteins of EV71 (e.g., hnRNP K, reticulon 3 (RTN 3)). In that work, researchers used a competitive assay to show that hnRNP K can interact with EV71 5' UTR, which is required for efficient synthesis of viral RNA. Using a yeast two-hybrid system, other researchers demonstrated that RTN 3 interacts with the N-terminal domain of EV71 2C, which is crucial for replication of viral RNA. Here, we discuss recent work focusing on the molecular mechanisms of hnRNP K and RTN 3 in the synthesis of the RNA and proteins of EV71.
Animals ; Carrier Proteins ; genetics ; metabolism ; Enterovirus A, Human ; genetics ; physiology ; Enterovirus Infections ; genetics ; metabolism ; virology ; Heterogeneous-Nuclear Ribonucleoprotein K ; Host-Pathogen Interactions ; Humans ; Membrane Proteins ; genetics ; metabolism ; Nerve Tissue Proteins ; genetics ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Viral Proteins ; genetics ; metabolism ; Virus Replication

OBJECTIVETo identify and compare the expression profiles of differential proteins between chronic phase and blast crisis in chronic myeloid leukemia (CML) by proteomic analysis, and screen the proteins related to blast crisis.

METHODSThe total cellular proteins from the bone marrow cells at chronic phase (CP) and blast crisis (BC) in CML were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and analyzed with ImageMaster 5.0 software to screen the differential protein spots. Differential protein spots were identified by mass spectrometry for peptide mass fingerprint in combination with database searching from SWISS-PROT. Then 3 protein spots were selected to verify at protein and mRNA levels by Western blot and semi-quantitative RT-PCR, separately.

RESULTSComparing gel pages from CML-CP and CML-BC, the expression of 13 protein spots decreased and 25 protein spots increased significantly in CML-BC. Twenty differential protein spots were identified by mass spectrometry and 15 were successfully determined. The results of Western blotting were similar to those of 2-DE and showed a high expression of hnRNPK, annexin A1 and RhoA. Semi-quantitative RT-PCR analysis showed that there was no correlation between the protein expression changes and mRNA levels of hnRNPK, annexin A1 and RhoA.

CONCLUSIONA group of proteins associated with blast crisis are obtained and the results may provide clues for further research to elucidate the role of these proteins in CML-BC carcinogenesis and to develop potential associated biomarkers.

Adult ; Aged ; Annexin A1 ; genetics ; metabolism ; Blast Crisis ; genetics ; metabolism ; Female ; Gene Expression Profiling ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Leukemia, Myeloid, Chronic-Phase ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Proteomics ; methods ; RNA, Messenger ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Young Adult ; rhoA GTP-Binding Protein ; genetics ; metabolism

OBJECTIVETumor 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.

METHODSNuclear 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.

RESULTSPreviously, 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.

CONCLUSIONTaken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.

Apoptosis ; physiology ; Cell Line, Tumor ; Gene Expression Regulation ; physiology ; Heterogeneous-Nuclear Ribonucleoprotein K ; genetics ; metabolism ; Humans ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; Up-Regulation ; physiology ; X-Linked Inhibitor of Apoptosis Protein ; genetics ; metabolism

OBJECTIVETo investigate the expression feature of heterogeneous nuclear ribonucleoprotein K in gastric carcinoma and its clinical significance, and to explore the relationship between hnRNPK expression and Helicobacter pylori L-form infection.

METHODSThe expression of hnRNPK protein was examined in 100 cases of gastric carcinoma, 50 paracancerous gastric tissues and 30 matched normal gastric mucosa by Elivision immunohistochemistry and hnRNPK-mRNA by in situ hybridization. Hp-L was detected with Gram staining and immunohistochemical staining.

RESULTSThe positive rates of hnRNPK protein and mRNA in gastric carcinoma were 82.0% and 86.0%, respectively, significantly higher than those in the paracancerous gastric tissues and normal controls (P < 0.05). The expression of hnRNPK protein was significantly correlated with histological differentiation, TNM stage and lymph node metastasis (P < 0.05). The positive rates of Hp-L in the three groups were 67.0%, 58.0% and 23.3%, respectively. The positive rate of Hp-L in gastric carcinoma had no significant correlation with it in the paracancerous gastric tissues, but was significantly higher than it in the normal controls (P < 0.05). In gastric carcinoma, the expression of hnRNPK protein was higher in cases of Hp-L positive patients than those of Hp-L negative cases (P < 0.05). Positive correlation existed between the expression of hnRNPK protein and Hp-L infection (r = 0.391, P < 0.01).

CONCLUSIONSThere is a higher expression of hnRNPK in gastric carcinoma. Hp-L infection may be associated with the up-regulated hnRNPK expression. The two factors may play a synergetic role in gastric carcinogenesis.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastric Mucosa ; metabolism ; Helicobacter Infections ; metabolism ; microbiology ; Helicobacter pylori ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Precancerous Conditions ; metabolism ; microbiology ; pathology ; RNA, Messenger ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Stomach Neoplasms ; metabolism ; microbiology ; pathology