ABSTRACT
OBJECTIVES: Lung cancer was one of the most common malignancies around the world. It has great significance in to search for the mechanism of occurrence and development of lung cancer. LIM Domain Binding protein 2 (LDB2) belongs to the LIM-domain binding family, it can be used as a binding protein that combined with other transcription factors to form the transcription complex for regulating the expression of target genes. The expression of microRNA-96-5p (miR-96-5p) has been investigated in various tumors. The aim of this study is to investigate the potential role of LDB2 and miR-96-5p in lung cancer. METHODS: Real-time quantitative PCR was applied to detect the expression of LDB2 and miR-96-5p. The proliferation, invasion, and metastasis of H1299 cells were analyzed by CCK8, transwell, and wound healing assay after LDB2 or miR-96-5p transfection. Luciferase activities assay and western blot were used to reveal the targeted regulation between LDB2 and miR-96-5p. RESULTS: Here the authors found LDB2 was down-regulated in lung cancer tissues and negatively correlated with miR-96-5p expression, it could promote or inhibit the proliferation, invasion and metastasis of H1299 cells after LDB2 knockdown or overexpression and regulate the expression of cyclinD1, MMP9, Bcl-2, and Bax via ERK1/2 signaling pathway. Furthermore, miR-96-5p exerted its function by directly binding to 3'-UTR of LDB2 and regulating expression of LDB2. miR-96-5p could promote the proliferation, invasion, and metastasis of H1299 cells. CONCLUSION: These findings demonstrate that LDB2 can act as a new regulator to inhibit cell proliferation, invasion, and metastasis via the ERK1/2 signaling pathway, and miR-96-5p may be a potential promising molecular by targeting LDB2 in lung cancer.
Subject(s)
Lung Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , Cell Line, Tumor , Neoplasm Invasiveness/genetics , Cell Movement/genetics , Lung Neoplasms/pathology , Cell Proliferation/genetics , 3' Untranslated Regions , Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , LIM Domain Proteins/genetics , LIM Domain Proteins/metabolismABSTRACT
Abstract Objective The study explored improvements in pulmonary inflammation and fibrosis in a bovine type II collagen-induced rheumatoid arthritis-associated interstitial lung disease mouse model after treatment with baricitinib and the possible mechanism of action. Methods A rheumatoid arthritis-associated interstitial lung disease mouse model was established, siRNA Jak2 and lentiviral vectors were transfected with human embryonic lung fibroblast cells. And the levels of relevant proteins in mouse lung tissue and human embryonic lung fibroblasts were detected by Western blotting. Results The levels of JAK2, p-JAK2, p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were increased in the lung tissues of model mice (P < 0.5) and decreased after baricitinib intervention (P < 0.05). The expression levels of p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were reduced after siRNA downregulation of the JAK2 gene (P < 0.01) and increased after lentiviral overexpression of the JAK2 gene (P < 0.01). Conclusion Baricitinib alleviated fibrosis in the lung tissue of rheumatoid arthritis-associated interstitial lung disease mice, and the mechanism of action may involve the downregulation of Smad3 expression via inhibition of the Jak2/Stat3 signaling pathway, with consequent inhibition of the profibrotic effect of transforming growth factor-β1.
ABSTRACT
Abstract Objectives: Lung cancer was one of the most common malignancies around the world. It has great significance in to search for the mechanism of occurrence and development of lung cancer. LIM Domain Binding protein 2 (LDB2) belongs to the LIM-domain binding family, it can be used as a binding protein that combined with other transcription factors to form the transcription complex for regulating the expression of target genes. The expression of microRNA-96-5p (miR-96-5p) has been investigated in various tumors. The aim of this study is to investigate the potential role of LDB2 and miR-96-5p in lung cancer. Methods: Real-time quantitative PCR was applied to detect the expression of LDB2 and miR-96-5p. The proliferation, invasion, and metastasis of H1299 cells were analyzed by CCK8, transwell, and wound healing assay after LDB2 or miR-96-5p transfection. Luciferase activities assay and western blot were used to reveal the targeted regulation between LDB2 and miR-96-5p. Results: Here the authors found LDB2 was down-regulated in lung cancer tissues and negatively correlated with miR-96-5p expression, it could promote or inhibit the proliferation, invasion and metastasis of H1299 cells after LDB2 knockdown or overexpression and regulate the expression of cyclinD1, MMP9, Bcl-2, and Bax via ERK1/2 signaling pathway. Furthermore, miR-96-5p exerted its function by directly binding to 3′-UTR of LDB2 and regulating expression of LDB2. miR-96-5p could promote the proliferation, invasion, and metastasis of H1299 cells. Conclusion: These findings demonstrate that LDB2 can act as a new regulator to inhibit cell proliferation, invasion, and metastasis via the ERK1/2 signaling pathway, and miR-96-5p may be a potential promising molecular by targeting LDB2 in lung cancer.
ABSTRACT
OBJECTIVE: This study investigated serum interleukin-10 (IL-10) levels, changes in peripheral blood CD4+CD25+ regulatory T cell (PBCDT) ratios, and the prognosis of cervical cancer (CC) patients. METHODS: Seventy patients with CC composed the observation group, and 70 healthy subjects composed the control group. The PBCDT ratios in the CC patients and healthy subjects were calculated. Serum IL-10 levels were detected with a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The PBCDT ratio was higher in the patients with active CC [12.16±2.41%] than in the control subjects [6.34±1.05%]. Serum IL-10 levels were higher in the patients with CC [384±106 pg/ml] than in the control subjects [104±50 pg/ml]; the differences in both PBCDT ratio and IL-10 level were statistically significant (p<0.01). Serum IL-10 levels were positively correlated with PBCDT ratios (r=0.375, p<0.05). The 5-year patient survival rate was significantly higher in the low serum IL-10 group (64.2%) than in the high serum IL-10 group (42.8%, p=0.012). CONCLUSIONS: PBCDT ratios and serum IL-10 levels are related to CC activity. These factors are reciprocally related and influence one another, and both are involved in the development and progression of CC. Low IL-10 expression is beneficial regarding the survival of patients with CC.
Subject(s)
Antigens, CD/blood , Interleukin-10/blood , T-Lymphocytes, Regulatory/cytology , Uterine Cervical Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Interleukin-10/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Prognosis , Socioeconomic Factors , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/virologyABSTRACT
OBJECTIVE: This study investigated serum interleukin-10 (IL-10) levels, changes in peripheral blood CD4+CD25+ regulatory T cell (PBCDT) ratios, and the prognosis of cervical cancer (CC) patients. METHODS: Seventy patients with CC composed the observation group, and 70 healthy subjects composed the control group. The PBCDT ratios in the CC patients and healthy subjects were calculated. Serum IL-10 levels were detected with a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The PBCDT ratio was higher in the patients with active CC [12.16±2.41%] than in the control subjects [6.34±1.05%]. Serum IL-10 levels were higher in the patients with CC [384±106 pg/ml] than in the control subjects [104±50 pg/ml]; the differences in both PBCDT ratio and IL-10 level were statistically significant (p<0.01). Serum IL-10 levels were positively correlated with PBCDT ratios (r=0.375, p<0.05). The 5-year patient survival rate was significantly higher in the low serum IL-10 group (64.2%) than in the high serum IL-10 group (42.8%, p=0.012). CONCLUSIONS: PBCDT ratios and serum IL-10 levels are related to CC activity. These factors are reciprocally related and influence one another, and both are involved in the development and progression of CC. Low IL-10 expression is beneficial regarding the survival of patients with CC.