Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer

Abstract Background This study aimed to evaluate the possible role of human papillomavirus (HPV) and Epstein–Barr virus (EBV) coinfection as an etiological factor for prostate cancer (PCa) development. Methods This case-control study was conducted on 67 patients with PCa and 40 control subjects. The expression levels of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantified, using the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assay. Results The EBV/HPV coinfection was reported in 14.9% of patients in the case group and 7.5% of the control subjects. The high-risk types of HPV, that is, HPV 16 and HPV 18, were responsible for 50 and 30% of HPV/EBV-coinfected PCa cases (n = 10), respectively. No significant relationship was observed between PCa and HPV/EBV coinfection (OR = 2.9, 95% CI: 0.18–45.2, P = 0.31). However, the highest percentage of HPV genome integration was found in the HPV/EBV-coinfected PCa group (8/10; 80%). Also, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS, and RNS), anti-apoptotic mediators (Bcl-2 and survivin), and anti-anoikis factors (Twist and N-cadherin) were significantly higher in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Nevertheless, the tumor-suppressor proteins (p53 and pRb) and E-cadherin (inhibitor of anoikis resistance) showed significant downregulations in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Conclusion The HPV/EBV coinfection may be an etiological factor for PCa through modulation of cellular behaviors.

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Anoikis Resistance and Development in Prostate Cancer: The Possible Role of HPV/EBV Coinfection

10.21203/rs.3.rs-135451/v1 ◽

2021 ◽

Author(s):

Javid Sadri Nahand ◽

Khadijeh Khanaliha ◽

Hamed Mirzaei ◽

Mohsen Moghoofei ◽

Hossein Bannazadeh Baghi ◽

...

Keyword(s):

Prostate Cancer ◽

Inflammatory Factors ◽

Control Group ◽

Etiologic Factor ◽

Case Group ◽

Anoikis Resistance ◽

Cellular Behavior ◽

Control Research ◽

High Risk Type

Abstract Background: This study aimed to evaluate the possible role of EBV/HPV co-infection as an etiologic factor in prostate cancer (PCa) development.Methods: The present case‐control research was conducted on 67 cases with prostate cancer and 40 controls. The expression of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantitated using ELISA and qRT-PCR.Results: The EBV/HPV co-infection was reported in 14.9% of case group and 7.5% of control group. The high-risk type of HPV, including HPV 16 and 18, were responsible for 50% and 30% of 10 HPV/EBV co-infected PCa samples, respectively. According to the results, a significant relationship was not observed between the PCa and HPV/EBV co-infection (OR=2.9, 95%CI=0.18-45.2, P=0.31). However, the highest percentage of HPV genome integration was found in HPV/EBV coinfected PCa group (8/10, 80%). Moreover, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS and RNS), anti-apoptotic mediators (Bcl-2 and Survivin), and anti-anoikis factors (TWIST, N-cad) were higher significantly in the HPV/EBV co-infected PCa cases when comparing with the non-coinfected PCa samples. Nevertheless, the tumor suppressor proteins (p53 and Rb) and the E-cad (inhibiting anoikis resistance) had a significant downregulation in the HPV/EBV co-infected PCa cases than in the non-coinfected PCa samples. Conclusion: HPV/EBV co-infection probably can act as an etiologic factor in PCa through modulation of cellular behavior.

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The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer

Journal of International Medical Research ◽

10.1177/03000605211014363 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110143

Author(s):

Mingcui Zang ◽

Xun Guo ◽

Manqiu Chen

Keyword(s):

Prostate Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Prostate Tumorigenesis ◽

Expression Levels ◽

Matrigel Invasion ◽

Tensin Homolog ◽

Docetaxel Treatment ◽

Induced Apoptosis

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

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Correlation between expression levels of IL-37, GM-CSF, and CRP in peripheral blood and atherosclerosis and plaque stability

European Journal of Inflammation ◽

10.1177/2058739219844068 ◽

2019 ◽

Vol 17 ◽

pp. 205873921984406

Author(s):

Tao Zheng ◽

Qingyun Zhou ◽

Zhe Chen ◽

Qinning Wang

Keyword(s):

Peripheral Blood ◽

Density Lipoprotein ◽

Inflammatory Factors ◽

Control Group ◽

Case Group ◽

Expression Levels ◽

Gm Csf ◽

Significant Difference ◽

Group A ◽

Group B

The study aimed to study the correlation between expression levels of interleukin-37 (IL-37), granulocyte macrophage colony-stimulating factor (GM-CSF), and C-reactive protein (CRP) in peripheral blood and the status of atherosclerosis (AS) and plaque stability and to confirm the clinical significance of these inflammatory factors in the pathogenesis of AS. A total of 64 AS patients (case group) were selected and divided into unstable plaque group (group A, 28 cases) and stable plaque group (group B, 36 cases) according to the color ultrasonography results of arterial vessels. At the same time, 30 healthy subjects were classified into the control group. General information of the enrolled subjects was collected, including levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), CRP, and homocysteine (Hcy). The expression levels of IL-37 and GM-CSF in the serum of peripheral blood samples collected from these subjects were measured by enzyme-linked immunosorbent assay (ELISA). There was no significant difference between the case group and the control group in the levels of TC, TG, HDL, and LDL ( P > 0.05). However, the expression level of Hcy in the case group was significantly higher than that in the control group ( P < 0.05). Compared with the control group, the expression levels of IL-37, GM-CSF, and CRP in the case group were significantly increased ( P < 0.05). In addition, compared with group B, the expression level of GM-CSF in group A was significantly increased ( P < 0.05), while no significant difference was detected between group A and group B in the expression levels of IL-37 and CRP ( P > 0.05). In conclusion, inflammatory factors IL-37, GM-CSF, CRP, and Hcy were all involved in the pathogenesis of AS, and the increased levels of GM-CSF were closely related to the progress of unstable plaques. These results may aid the early diagnosis/treatment of AS.

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Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000477118 ◽

2017 ◽

Vol 42 (1) ◽

pp. 91-102 ◽

Cited By ~ 7

Author(s):

Xin Xue ◽

Yi Qiu ◽

Hong-Li Yang

Keyword(s):

Cell Viability ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Inflammatory Factors ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Bacillus Calmette Guerin ◽

Myd88 Signaling ◽

Apoptosis And Necrosis

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.

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Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

10.21203/rs.2.16055/v3 ◽

2020 ◽

Author(s):

Yi Yang ◽

Ran Luo ◽

Yichun Cheng ◽

Tingting Liu ◽

Wei Dai ◽

...

Keyword(s):

Renal Function ◽

Lupus Nephritis ◽

Disease Activity ◽

Peripheral Blood ◽

Enzyme Linked Immunosorbent Assay ◽

Epithelial Cell Line ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Expression Levels

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1. Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.

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Effects of human umbilical cord mesenchymal stem cells on inflammatory factors and miR-181a in T lymphocytes from patients with systemic lupus erythematosus

Lupus ◽

10.1177/0961203319896417 ◽

2019 ◽

Vol 29 (2) ◽

pp. 126-135

Author(s):

B Zheng ◽

P Zhang ◽

L Yuan ◽

R K Chhetri ◽

Y Guo ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

T Lymphocytes ◽

Umbilical Cord ◽

Lupus Erythematosus ◽

Inflammatory Factors ◽

Enzyme Linked Immunosorbent Assay ◽

Human Umbilical Cord ◽

Expression Levels ◽

Gene And Protein Expression

Objectives The present study aimed to explore the effect of umbilical cord mesenchymal stem cells (UC-MSCs) on the modulation of T lymphocytes from system lupus erythematosus (SLE) patients and the possible mechanism. Methods A total of 24 hospitalized SLE patients and 28 healthy individuals were enrolled. T lymphocytes were sorted using Miltenyi magnetic beads. After the addition of recombinant human interleukin (IL)-2 and CD3CD28 T-cell activator, cells were loaded onto six-well plates pre-inoculated or not with UC-MSCs for 1 week of culture. The supernatants were collected for testing inflammatory factors by enzyme-linked immunosorbent assay. Meanwhile, T lymphocytes were collected to assess the expression levels of genes, proteins in relation to SLE and miR-181a by polymerase chain reaction and Western blot. Results Compared with T lymphocytes cultured alone, interferon-γ, IL-4, IL-6 and IL-10 levels were significantly decreased in T lymphocytes from SLE patients co-cultured with UC-MSCs. In addition, the gene and protein expression levels of TNF alpha, osteopontin and nuclear factor-kappa B in T lymphocytes were significantly decreased, while miR-181a expression was markedly elevated ( p < 0.05 or 0.008). Conclusion UC-MSCs have showed certain immunomodulatory and inhibitory effects in vitro on T lymphocytes from SLE patients, which could potentially be a beneficial treatment of the disease. UC-MSCs may up-regulate miR-181a and down-regulate inflammation-related gene expression.

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Estrogen is an important mediator of mast cell activation in ovarian endometriomas

Reproduction ◽

10.1530/rep-17-0457 ◽

2018 ◽

Vol 155 (1) ◽

pp. 73-83 ◽

Cited By ~ 8

Author(s):

Tian-Hong Zhu ◽

Shao-Jie Ding ◽

Tian-Tian Li ◽

Li-Bo Zhu ◽

Xiu-Feng Huang ◽

...

Keyword(s):

Growth Factor ◽

Transient Receptor Potential ◽

Transforming Growth Factor ◽

Biologically Active ◽

Mast Cell Activation ◽

Enzyme Linked Immunosorbent Assay ◽

Expression Levels ◽

Endometrial Cells ◽

Ovarian Endometriomas

Endometriosis is an estrogen-dependent disease. Previous research has shown that abnormal enzymes associated with estrogen (E2) metabolism and an increased number of mast cells (MCs) in endometriomas are implicated in the pathogenesis of endometriosis. However, it remains unclear how MCs mediate the role of E2 in endometriosis. Accordingly, we investigated whether E2 was associated with the number of MCs, and the rate of degranulation, in local ovarian endometriomas, as well as the role of E2 on MCs during the pathogenesis of endometriosis. Using enzyme-linked immunosorbent assay and immunohistochemistry, we found that concentrations of E2, and the number and activity of MCs, were significantly higher in ovarian endometriomas than in controls, and that these parameters were correlated with the severity of endometriosis-associated dysmenorrhea. By measuring the release of hexosaminidase, we found that the rate of RBL2H3 cell degranulation increased after E2 treatment. Furthermore, activation of RBL2H3 cells by E2 was found to trigger the release of biologically active nerve growth factor, which promotes neurite outgrowth in PC12 cells and also sensitizes dorsal root ganglion cells via upregulation ofNav1.8and transient receptor potential cation channel (subfamily V member 1) expression levels. When treated with E2, endometriotic cells could promote RBL2H3 cell recruitment by upregulating expression levels of stem cell factor, transforming growth factor-β and monocyte chemoattractant protein-1; these observations were not evident with control endometrial cells. Thus, elevated E2 concentrations may be a key factor for degranulation and recruitment of MCs in ovarian endometriomas, which play a key role in endometriosis-associated dysmenorrhea.

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Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

10.21203/rs.2.16055/v2 ◽

2020 ◽

Author(s):

Yi Yang ◽

Ran Luo ◽

Yichun Cheng ◽

Tingting Liu ◽

Wei Dai ◽

...

Keyword(s):

Renal Function ◽

Lupus Nephritis ◽

Disease Activity ◽

Peripheral Blood ◽

Enzyme Linked Immunosorbent Assay ◽

Epithelial Cell Line ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Expression Levels

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Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity

Cancer Cell International ◽

10.1186/s12935-020-01583-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jialin Zhu ◽

Yan Wang ◽

Dai Li ◽

Haonan Zhang ◽

Zhi Guo ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

T Cells ◽

Cd8 T Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tumour Immunity ◽

Immunohistochemical Stains

Abstract Background Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. Methods The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound‐healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry. Results High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role. Conclusions IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.

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Production of Interferons and β-Chemokines by Placental Trophoblasts of HIV-1-Infected Women

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/s1064744901000175 ◽

2001 ◽

Vol 9 (2) ◽

pp. 95-104 ◽

Cited By ~ 16

Author(s):

Bang-Ning Lee ◽

Hunter Hammill ◽

Edwina J. Popek ◽

Stanley Cron ◽

Claudia Kozinetz ◽

...

Keyword(s):

Enzyme Linked Immunosorbent Assay ◽

Control Subjects ◽

Trophoblastic Cells ◽

Inflammatory Protein ◽

Β Protein ◽

Immunodeficiency Virus ◽

Vertical Transmission Of Hiv ◽

And Control ◽

Hiv 1

Objective:The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the β-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-α (MIP-1α), and MIP-1β can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptorCCR5. In this study the production of IFNs and β-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined.Methods:Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and β-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-β transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay.Results:All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-α and IFN-γ produced by trophoblasts of HIV-1- infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-β protein than trophoblasts of control subjects. Furthermore, the median levels of β-chemokines produced by trophoblasts of HIV-infected and control women were similar.Conclusions:Since there was no correlation between the placental HIV load and the production of interferons or β-chemokines, the role of trophoblast-derived IFNs and β-chemokines in protecting the fetus from infection with HIV-1 is not clear.

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