Reproductive Hormones and Their Receptors May Affect Lung Cancer

Background/Aims: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. Methods: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERβ (oestrogen receptor β) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERβ were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. Results: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized group, while the E2/T ratio increased compared with the control group (E2: 55.88±11.45 and 78.21±9.37; T: 0.82±0.14 and 1.46±0.16; ratio: 69.62±14.43±29.81 and 52.22±5.42; all P<0.05). The Western blot and IHC results indicated that AR, ERα and ERβ protein expression levels were obviously higher in transplanted tumour and lung tissues from the ovariectomized group, with particular increases in ERβ in transplanted tumour tissue and in ERα in lung tissue. The PCR results also showed markedly higher mRNA expression levels of AR, ERα and ERβ in the ovariectomized group, and in particular, ERβ in transplanted tumour tissue and ERα in lung tissue were significantly increased in the ovariectomized group. Conclusion: Ovariectomy decreased E2 and T serum levels and increased the E2/T ratio in mice, and this imbalance in the internal environment promoted the growth of transplanted tumours. Sex hormone disorder not only promoted transplanted tumour growth but also significantly reduced the protein and mRNA expression levels of sex hormone receptors. The metabolism of E2 and T may affect the growth, proliferation and metabolism of lung cancer cells, and the mechanism by which sex hormones and their receptors influence lung cancer is worthy of further research.

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Comprehensive analysis of inhibitor of differentiation/DNA-binding gene family in lung cancer using bioinformatics methods

Bioscience Reports ◽

10.1042/bsr20193075 ◽

2020 ◽

Vol 40 (2) ◽

Cited By ~ 2

Author(s):

Suming Xu ◽

Yaoqin Wang ◽

Yanhong Li ◽

Lei Zhang ◽

Chunfang Wang ◽

...

Keyword(s):

Lung Cancer ◽

Transcription Factor ◽

Dna Binding ◽

Mrna Expression ◽

Family Members ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Genetic Mutations ◽

Expression Levels ◽

Mrna Expression Levels

Abstract The inhibitor of differentiation/DNA-binding (ID) is a member of the helix–loop–helix (HLH) transcription factor family, and plays a role in tumorigenesis, invasiveness and angiogenesis. The aims were to investigate the expression patterns and prognostic values of individual ID family members in lung cancer, and the potential functional roles. The expression levels of ID family were assessed using the Oncomine online database and GEPIA database. Furthermore, the prognostic value of ID family members was evaluated using the Kaplan–Meier plotter database. The genetic mutations of ID family members were investigated using the cBioPortal database. Moreover, enrichment analysis was performed using STRING database and Funrich software. It was found that all the ID family members were significantly down-regulated in lung cancer. Prognostic results indicated that low mRNA expression levels of ID1 or increased mRNA expression levels of ID2/3/4 were associated with improved overall survival, first progression and post progression survival. Additionally, genetic mutations of ID family members were identified in lung cancer, and it was suggested that amplification and deep deletion were the main mutation types. Furthermore, functional enrichment analysis results suggested that ID1/2/4 were significantly enriched in ‘regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism’ for biological process, ‘transcription factor activity’ for molecular function and ‘HLH domain’ for protein domain. However, it was found that ID3 was not enriched in the above functions. The aberrant expression of ID family members may affect the occurrence and prognosis of lung cancer, and may be related to cell metabolism and transcriptional regulation.

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Clinical Usefulness of Monitoring Expression Levels ofCCL24(Eotaxin-2) mRNA on the Ocular Surface in Patients with Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis

Journal of Ophthalmology ◽

10.1155/2016/3573142 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

Yukiko Shiraki ◽

Jun Shoji ◽

Noriko Inada

Keyword(s):

Mrna Expression ◽

Ocular Surface ◽

Clinical Score ◽

Clinical Severity ◽

Vernal Keratoconjunctivitis ◽

Control Group ◽

Expression Levels ◽

Atopic Keratoconjunctivitis ◽

Clinical Scores ◽

Mrna Expression Levels

Purpose. This study aimed to evaluate the clinical efficacy of using expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface as a biomarker in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).Methods. Eighteen patients with VKC or AKC (VKC/AKC group) and 12 control subjects (control group) were enrolled in this study. The VKC/AKC clinical score was determined by objective findings in patients by using the 5-5-5 exacerbation grading scale. All subjects underwent modified impression cytology and specimens were obtained from the upper tarsal conjunctiva. Expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface were determined using real-time reverse transcription polymerase chain reaction.Results. The VKC group was divided into two subgroups, depending on the clinical score: the active stage subgroup with 100 points or more of clinical scores and the stable stage subgroup with 100 points or less.CCL24(eotaxin-2) mRNA expression levels in the active VKC/AKC stage subgroup were significantly higher than those in the stable VKC/AKC subgroup and the control group. Clinical scores correlated significantly withCCL24(eotaxin-2) mRNA expression levels in the VKC group.Conclusions.CCL24(eotaxin-2) mRNA expression levels on the ocular surface are a useful biomarker for clinical severity of VKC/AKC.

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HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920917562 ◽

2020 ◽

Vol 12 ◽

pp. 175883592091756

Author(s):

Jing-Hua Yang ◽

Ming-Zhe Wu ◽

Xu-Bo Wang ◽

Shiyu Wang ◽

Xue-Shan Qiu ◽

...

Keyword(s):

Lung Cancer ◽

Mrna Expression ◽

Gene Amplification ◽

Genetic Manipulation ◽

Mrna Levels ◽

Promoter Regions ◽

Hpv16 E6 ◽

Expression Levels ◽

Malignant Group ◽

Mrna Expression Levels

Background: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. Materials & Methods: A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines. Results: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression. Conclusion: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.

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Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v110.11.3847.3847 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3847-3847 ◽

Cited By ~ 1

Author(s):

Yunfeng Cheng ◽

Shanhua Zou ◽

Feng Li

Keyword(s):

Plasma Concentration ◽

Mrna Expression ◽

Mononuclear Cells ◽

Control Group ◽

Gene Expressions ◽

Expression Levels ◽

Tnf Α ◽

Healthy Control ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

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Cytokine Gene Expression and IgA Production in the Spleen of Chickens Infected with Eimeria tenella

Indian Journal of Animal Research ◽

10.18805/ijar.b-1188 ◽

2020 ◽

Cited By ~ 1

Author(s):

Liushu Jia ◽

Bianhua Zhou ◽

Hongwei Wang ◽

Fan Yang ◽

Guoyong Wang ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Morphological Characteristics ◽

Eimeria Tenella ◽

Cytokine Gene Expression ◽

Control Group ◽

Expression Levels ◽

New Strategy ◽

Iga Production ◽

Mrna Expression Levels

To explore the effect of Eimeria tenella infection on the cytokines gene expression and IgA production in the spleen of chickens, the morphological characteristics of the spleen were observed through optical and transmission electron microscopy. The IgA production was determined through immunohistochemistry. The mRNA expression levels of splenic cytokines were detected through real-time PCR. Compared to the control group, along with the infection of E. tenella, the splenic lymphocytes exhibited irregular and cracked membranes, mitochondria swelled even vacuolization, the IgA expression in spleen tissue was decreased by 55.57% (p lessthan 0.01). Likewise, the mRNA expression levels of IL-2 and IL-1â decreased by 40% (plessthan 0.01) and 43% p lessthan 0.05), respectively. By contrast, the IL-6, IFN-g and IL-10 levels increased by 158% (p lessthan 0.01), 464% (p lessthan 0.05) and 379% p lessthan 0.01), respectively. These results indicated that the spleen implement an important function in the antagonism of E. tenella, which suggest a new strategy to control coccidiosis by improving the peripheral immunity of chickens.

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Effect of Short-Term Endurance Exercise on COX IV and PGC-1a mRNA Expression Levels in Rat Skeletal Muscle

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1759 ◽

2019 ◽

Vol 12 (3) ◽

pp. 1309-1316 ◽

Cited By ~ 1

Author(s):

Nova Sylviana ◽

Christina Natalia ◽

Hanna Goenawan ◽

Yuni Susanti Pratiwi ◽

Iwan Setiawan ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Endurance Exercise ◽

Mitochondrial Biogenesis ◽

Control Group ◽

Muscle Adaptation ◽

Rat Skeletal Muscle ◽

Short Term ◽

Expression Levels ◽

Mrna Expression Levels

Endurance exercise induces specific skeletal muscle adaptation by increasing mitochondrial oxidative phosphorylation eficiency and mitochondrial biogenesis. Many previous studies suggesting both PGC-1a and COX IV as a potential biomarker of skeletal muscle adaptation induced by exercise. But most of them only studied the effect of long-term endurance exercise, whereas the effect of short-term exercise remains unclear. To investigate short-term physiological adaptation induced by endurance exercise on expression of COX IV and PGC-1a mRNA in rat skeletal muscle. Twenty healthy male Wistar rats (Rattus norvegicus) aged 10-11 weeks old were used in this experiment. Rats were randomly assigned into 4 groups based on the time period of exercise: 1) control (C; n=5), 2) three days of exercise (E3; n=5), 3) six days of exercise (E6; n=5), 4) fifteen days of exercise (E15; n=5). The exercise groups were run at 20m/s for 30 minutes on the rat treadmill and the stationary control group was only placed inside treadmill with the machines turned off. On the last day of exercise, the rats were sacrificed then RNA from skeletal muscle was extracted. COX IV and PGC-1a mRNA expressions were measured by Reverse Transcriptase PCR. The results showed that there were statistically significant differences of PGC-1a mRNA expression levels in both soleus (F(3,16)=3.740, ps=0.033) and gastrocnemius (F(3,16)=3.969, pg=0.027) muscles. The COX IV mRNA expression levels in soleus (F(3,16)=3.801, ps=0.031) and gastrocnemius (F(3,16)=5.429, ps=0.009) muscles were also significantly increased. There were significant increases of PGC-1a and COX IV expressions in fifteen days of exercise group compared to control group in both muscles. Short-term endurance exercise induced mitochondrial biogenesis marker and mitochondrial activity marker by increasing the PGC-1a and COX IV mRNA expression levels in rat skeletal muscle significantly following the time periods of exercise.

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Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Reproduction ◽

10.1530/rep-14-0567 ◽

2015 ◽

Vol 149 (6) ◽

pp. 645-655 ◽

Cited By ~ 15

Author(s):

Oscar E Rivera ◽

Jorgelina Varayoud ◽

Horacio A Rodríguez ◽

Clarisa G Santamaría ◽

Verónica L Bosquiazzo ◽

...

Keyword(s):

Estrogen Receptor ◽

Mrna Expression ◽

Estrogen Receptor Alpha ◽

Ovarian Function ◽

Steroid Receptors ◽

Ovarian Response ◽

Serum Levels ◽

Lower Number ◽

Expression Levels ◽

Mrna Expression Levels

Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 μg/kg per day, BPA0.5: 0.5 μg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17β-estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles ≥2 mm in diameter together with a lower number of atretic follicles and no increase in E2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood.

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The expression of Drosha, DGCR8, Dicer and Ago-2 genes are upregulated in human umbilical vein endothelial cells under hyperglycemic condition

Endocrine Regulations ◽

10.2478/enr-2018-0014 ◽

2018 ◽

Vol 52 (3) ◽

pp. 123-127 ◽

Cited By ~ 2

Author(s):

Farhad Ghadiri Soufi ◽

Ali Akbar Poursadegh Zonouzi ◽

Ebrahim Eftekhar ◽

Kamila Kamali ◽

Sara Aghakhani Chegeni ◽

...

Keyword(s):

Endothelial Cells ◽

Mrna Expression ◽

Umbilical Vein ◽

Control Group ◽

Human Umbilical Vein ◽

Expression Levels ◽

Expression Of Genes ◽

Mirnas Expression ◽

Umbilical Vein Endothelial Cells ◽

Mrna Expression Levels

AbstractObjectives. It has been shown that dysregulation of miRNAs expression contributes to the pathogenesis and progression of the diabetes and diabetes-related complications. Drosha, DGCR8, Dicer, and Ago-2 are involved in the miRNA maturation. The aim of the present study was to investigate the mRNA expression levels of these genes in the human umbilical vein endothelial cells (HUVECs) under hyperglycemic condition.Methods. HUVECs were cultured in normo-(5 mM) and hyperglycemic (25 mM) conditions for 24 h. As osmotic control, cells were treated with D-mannitol (25 mM, for 24 h). The mRNA expression levels of Drosha, DGCR8, Dicer and Ago-2 were evaluated using quantitative real-time PCR.Results. The expression level of Drosha, DGCR8, Dicer, and Ago-2 were increased in hyperglycemic HUVECs compared to the control group.Conclusion. Our results show that under hyperglycemic condition, expression of genes involved in the miRNA maturation was significantly increased in HUVECs. Upregulation of these genes may have role in diabetic complications through the dysregulation of the miRNA expression.

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LPA Gene Polymorphisms and Gene Expression Associated with Coronary Artery Disease

BioMed Research International ◽

10.1155/2017/4138376 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Zi-Kai Song ◽

Hong-Yan Cao ◽

Hai-Di Wu ◽

Li-Ting Zhou ◽

Ling Qin

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Gene Polymorphisms ◽

Control Group ◽

Case Group ◽

Chinese Han ◽

Expression Levels ◽

Artery Disease ◽

Cad Risk ◽

Mrna Expression Levels

The aim of our study was to investigate the influence of LPA gene polymorphisms for CAD risk and Lp(a) in a case-control study of Chinese Han population. In addition, we further analyzed the effect of LPA gene expression on plasma levels of Lp(a) and CAD risk. First, five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in LPA gene were genotyped using the SEQUENOM Mass-ARRAY system in two groups. Second, we used quantitative real-time PCR to examine the mRNA expression levels of LPA gene in 92 cases and 32 controls. Results showed that the frequency of rs6415085-T allele was significantly higher in case group than that in control group (P<0.05). Haplotypes were not associated with CAD risk (P>0.05). And cases with the TT/TG genotype had significantly higher plasma Lp(a) levels compared with those that have the rs6415085 GG genotype (P<0.05). Additionally, the mRNA expression levels in case group are significantly higher than that in control group (P<0.05). Our study confirmed that rs6415085 was associated with CAD and increased plasma Lp(a) levels. And increased mRNA expression level of LPA gene may be a mechanism in development of CAD.

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Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2021/4005327 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Xieyi Zhang ◽

Wangyang Liu ◽

Kazue Edaki ◽

Yuta Nakazawa ◽

Hiroki Kamioka ◽

...

Keyword(s):

Lung Cancer ◽

Multidrug Resistance ◽

Mrna Expression ◽

Cancer Cells ◽

Transcriptional Regulators ◽

Scaffold Proteins ◽

Lung Cancer Cells ◽

Efflux Transporters ◽

Expression Levels ◽

Mrna Expression Levels

Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.

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