OBJECTIVETo investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells.

METHODSImmunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays. Western blotting, quantitative real-time PCR (qPCR) and immunofluorescence were used to assess the alterations of EMT markers in the cells with LKB1 knockdown.

RESULTSCompared with normal intestinal tissues, hamartoma polyps showed significantly decreased LKB1 and E-cadherin expressions and increased vimentin expression with increased collagen fiber deposition. The cells with LKB1 knockdown exhibited enhanced cell proliferation and migration activities (P<0.01). Western blot analysis, qPCR and immunofluorescence all detected decreased E-cadherin and increased N-cadherin, vimentin, Snail, and Slug expressions in the cells with LKB1 knockdown.

CONCLUSIONs LKB1 deficiency triggers EMT in intestinal epithelial cells and Peutz-Jeghers hamartoma, suggesting that EMT can serve as the therapeutic target for treatment of Peutz-Jeghers syndrome.

Animals ; Coronary Vessels ; surgery ; Drug-Eluting Stents ; adverse effects ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Sirolimus ; chemistry ; therapeutic use ; Swine

OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
Child ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Clinical Relevance ; Disease-Free Survival ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prednisone/therapeutic use* ; Prognosis ; Recurrence ; Immunoglobulin Light Chains, Surrogate/genetics*