ABSTRACT
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after kidney transplantation and specific characteristics of late-onset PJP have always been debated. METHODS: We performed a retrospective study by analysing the data of post-transplantation pneumonia in adult kidney transplantation recipients between March 2014 and December 2021 in The Affiliated First Hospital of University of Science and Technology of China (USTC). A total of 361 patients were included and divided into early-onset PJP, late-onset PJP and non-PJP groups. The characteristics of each group and related risk factors for the late-onset patients were investigated. RESULTS: Some patients developed PJP 9 months later with a second higher occurrence between month 10 and 15 after transplantation. Compared with non-PJP, ABO-incompatible and cytomegalovirus (CMV) viremia were significantly associated with late onset of PJP in multivariate analysis. The use of tacrolimus, CMV viremia, elevated CD8(+) T cell percent and hypoalbuminemia were risk factors for late PJP. Receiver operating characteristic curve analysis demonstrated that a combination of those factors could increase the sensitivity of prediction remarkably, with an area under the curve of 0.82, a sensitivity of 80% and a specificity of 83%. CONCLUSIONS: PJP could occur months after kidney transplantation. ABO-incompatible transplant recipients are at high risk of PJP. In the later stages of transplantation, CMV viremia, T lymphocyte subsets percentage and serum albumin levels should be monitored in patients using tacrolimus.
Subject(s)
Cytomegalovirus Infections , Kidney Transplantation , Pneumocystis carinii , Pneumonia, Pneumocystis , Adult , Humans , Pneumonia, Pneumocystis/drug therapy , Kidney Transplantation/adverse effects , Retrospective Studies , Transplant Recipients , Tacrolimus/therapeutic use , Viremia/complications , Risk Factors , Cytomegalovirus Infections/complicationsABSTRACT
Recent evidence shows that microRNAs (miRNAs) contribute to the biological effects of Toll-like receptor (TLR) signaling on various cells. Our previous data showed that TLR9 signaling could enhance the growth and metastatic potential of human lung cancer cells. However, the potential role of miRNAs in the effects of TLR9 signaling on tumor biology remains unknown. In this paper, we first report that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9 signaling-enhanced growth and metastatic potential of lung cancer cells in vitro and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3 (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western blotting and luciferase report assay. Further study shows that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in regulating the biological effects of TLR9 signaling on human lung cancer cells, which might be helpful to the understanding of the potential role of miRNAs in TLR signaling effects on tumor biology.
Subject(s)
Cell Proliferation , Lung Neoplasms/genetics , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Toll-Like Receptor 9/genetics , Animals , Blotting, Western , Cell Line, Tumor , Cell Movement , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Neoplasm Metastasis , Oligodeoxyribonucleotides/genetics , Oligodeoxyribonucleotides/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Toll-Like Receptor 9/metabolism , Xenograft Model Antitumor Assays/methodsABSTRACT
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Recent data suggested that IL-17 might be a pivotal cytokine involved in tumor progression of NSCLC. However, the direct effect of IL-17 on metastasis of NSCLC cells still remains intractable. In this study, we found that the metastasis of NSCLC was significantly impaired in IL-17â»/â» mice. Further, we revealed that IL-17 could directly promote the invasion of NSCLC cells both in vitro and in vivo. Furthermore, we found that IL-6-Stat3 pathway was crucial for IL-17 to enhance the invasive potential of NSCLC cells. Finally, we found that elevated expression of IL-17 in peripheral blood was associated with the TNM stage, and elevated expression of IL-17R in NSCLC cells was associated with their invasive potential in NSCLC patients. These findings could facilitate our understanding of the potential role of IL-17 in tumor biology, and provide clues for developing promising strategies against NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Interleukin-17/metabolism , Lung Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Interleukin-17/blood , Interleukin-17/genetics , Interleukin-6/metabolism , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Nude , Neoplasm Metastasis , Neoplasm Staging , Receptors, Interleukin-17/biosynthesis , Receptors, Interleukin-17/metabolism , STAT3 Transcription Factor/metabolism , Signal TransductionABSTRACT
High-mobility group box 1 (HMGB1) has been implicated in a variety of biologically important processes, including transcription, DNA repair, differentiation, development, and extracellular signaling. However, the potential role of HMGB1 in tumor biology still remains intractable. Our previous study showed that TLR9 response to CpG oligonucleotide (ODN) in 95D human lung cancer cells could enhance their growth and invasive potential in vitro and in vivo. Here we found that CpG ODN stimulation to 95D cells induced the secretion of HMGB1 in a dose dependent manner. We further showed that blockade of extracellular HMGB1 using A box peptide and ethyl pyruvate significantly abrogated the CpG ODN enhanced progression of 95D cells. Interestingly, we found that HMGB1 alone or acted synergistic with CpG ODN could enhance the progression of 95D cells. Notably, we revealed that RAGE and TLR4 were critical for HMGB1 to exert the synergistic function. We observed a MyD88-dependent upregulation of matrix metalloproteinase (MMP) 2, MMP9 and cyclin-dependent kinase (CDK) 2 in 95D cells in response to HMGB1. These findings might further our understanding of TLR9 signaling in tumor biology and be helpful for developing HMGB1-based strategy against lung cancer.
Subject(s)
Antineoplastic Agents/pharmacology , HMGB1 Protein/metabolism , Lung Neoplasms/drug therapy , Oligodeoxyribonucleotides/pharmacology , Cell Line, Tumor/drug effects , Cell Movement , Cell Proliferation , Cyclin-Dependent Kinase 2/metabolism , Gene Knockdown Techniques , HMGB1 Protein/antagonists & inhibitors , HMGB1 Protein/genetics , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Molecular Targeted Therapy , Myeloid Differentiation Factor 88/metabolism , Pyruvates/pharmacology , RNA Interference , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Signal Transduction , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 9/metabolism , Up-RegulationABSTRACT
BACKGROUND AND OBJECTIVE: Recent studies suggest that miR-155 is involved in lung tumorgenesis, whereas the precise mechanism has not yet been characterized. The aim of this study is to investigate the effects of over-expression of miR-155 on the growth of human lung cancer 95D cells in vitro and its possible mechanism, and thus to provide experimental evidence for further researching on the role of miR-155 in the pathogenesis and development of lung cancer. METHODS: miR-155 mimics control and miR-155 mimics were tranfected into human lung cancer 95D cells by FuGENE®HD Transfection Reagent respectively in vitro. The relative expression level of miR-155 in 95D cells was determined using specific probe of real-time PCR after transfection. The proliferation of 95D cells was detected by MTT assay. The cell cycle was analyzed by flow cytometry. The expression of SOS1 protein was measured by Western blot. RESULTS: Compared with control groups, the expression level of miR-155 was significantly increased in miR-155 mimics transfected group (P<0.05). The proliferation of miR-155-transfected 95D cells was significantly inhibited (P<0.05). The percentage of G0/G1 phase cells was increased significantly in miR-155-transfected 95D cells, while the percentage of S phase was remarkably reduced (P<0.05). Furthermore, the expression of SOS1 in miR-155-transfected 95D cells was significantly down-regulated (P<0.05). CONCLUSIONS: miR-155 could significantly inhibit the growth of human lung cancer 95D cells in vitro, which might be closely related to miR-155 induced G0/G1 phase arrest.