OBJECTIVE: To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells. METHODS: Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells. RESULTS: In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P < 0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P < 0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P < 0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P < 0.01). CONCLUSION CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.
Chemokines ; Coronary Angiography ; Coronary Artery Disease/genetics* ; Endothelial Cells ; Humans ; MARVEL Domain-Containing Proteins ; Tumor Suppressor Proteins

Objective: To investigate the mechanism of chemokine-like factor superfamily member (CMTM) 5 on the proliferation of multiple myeloma cells. Methods: RT-qPCR method was used to detect the expression and correlation of CMTM5, caspase3 and caspase9 in U266 after decitabine demethylation treatment; U266 transfected with pcDNA3.1 plasmid overexpressed CMTM5, then cell proliferation activity was detected by CCK-8 assay. Results: Compared with the control group, the low-dose demethylation treatment increased mRNA expression of CMTM5, caspase3, and caspase9 in U266, and showed a time-dependent (P<0.01). The up-trend of CMTM5, caspase3, and caspase9 in the high-demethylation drug treatment group was more significant and also showed time-dependent (P<0.001); There was a significant positive correlation between CMTM5 and caspase3 (r=0.937) and caspase9 (r=0.945) in each group (P<0.001). After transfection of U266 with the pcDNA3.1-CMTM5 plasmid, overexpression of CMTM5 inhibited the cell proliferation activity compared with the control and pcDNA3.1-vector group. Conclusion: Decitabine has a reductive effect on the low level of CMTM5 in U266 cells, and its recovery level is significantly positively correlated with caspase 3 and caspase9. Re-expression of CMTM5 inhibits the proliferative activity of U266.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Chemokines/genetics* ; Disease Progression ; Humans ; MARVEL Domain-Containing Proteins/genetics* ; Multiple Myeloma ; Transfection ; Tumor Suppressor Proteins/genetics*

Chemokine-like factor 1 (CKLF1) is a newly cloned chemotactic cytokine with CCR4 being its functional receptor. Recent evidence demonstrates a role of CKLF1 in arthritis. The aim of this study was to quantify the expression of CKLF1 as well as assess the correlation between CKLF1 and plasma acute-phase markers. Synovium was obtained from 16 osteoarthritis (OA), 15 rheumatoid arthritis (RA) and 10 ankylosing spondylitis (AS) patients undergoing total joint arthroplasty, with other 11 patients treated for meniscal tears during sport accidents serving as normal controls. Levels of CKLF1 and CCR4 mRNA were detected by qRT-PCR, and the expression of CKLF1 was investigated by immunohistochemistry staining, subsequently analyzed with semiquantitative scores. Plasma acute-phase markers of inflammation were determined by ELISA. CKLF1 was found with a particularly up-regulated expression in synovim from AS and RA patients, and CCR4 mRNA levels increased in RA patients, not in OA or AS patients. Elevated levels of plasma markers of inflammation including CRP, ESR and D-dimer were observed in RA. Further, significantly positive correlations between relative expression levels of CKLF1 and CRP/ESR in RA patients and a positive correlation between CKLF1 and ESR in AS patients were found. There was no detectable correlation between CKLF1 and plasma D-dimer. This study confirms an increased but different level of CKLF1 in RA, OA and AS patients, all significantly higher than that in controls. Additionally, the significant positive correlations between CKLF1 levels and CRP/ESR in RA and between CKLF1 and ESR suggest that CKLF1 might contribute to the inflammation state and clinical symptoms in these rheumatic diseases. Further studies are required to investigate the utility of targeting specific CKLF1 for symptom control or disease modification in RA and AS.
Adult ; Arthritis, Rheumatoid ; metabolism ; Biomarkers ; metabolism ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; metabolism ; Male ; Middle Aged ; Osteoarthritis ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Receptors, CCR4 ; genetics ; metabolism ; Spondylitis, Ankylosing ; metabolism ; Synovial Fluid ; metabolism

CKLF-like MARVEL transmembrane domain containing member/chemokine-like factor super family member (CKLFSF/CMTM) is a novel tumor suppressor gene. CMTM3 is broadly expressed in normal human tissues and evolutionary conserved,especially in testis,spleen,and some cells of peripheral blood mononuclear cells. However,its expression is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM3 may inhibit the proliferation,migration,and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear,CKLFSF3/CMTM3 is closely connected with immune system and associated with sex during tumorigenesis. The study advances of CKLFSF3/CMTM3 are elaborated in this review as CMTM3 may be a new target in the gene therapies for tumors,especially genitourinary tumors,while further studies on CMTM3 and its anti-tumor mechanisms are warranted.
Cell Transformation, Neoplastic ; Chemokines ; genetics ; physiology ; Down-Regulation ; Humans ; Leukocytes, Mononuclear ; MARVEL Domain-Containing Proteins ; genetics ; physiology ; Male ; Neoplasms ; pathology

OBJECTIVETo observe the effects of CMTM2 on cyclophosphamide (CP)-induced reproductive toxicity and the expression of steroidogenic acute regulatory (StAR) protein in the transgenic mouse model.

METHODSTwenty CMTM2 transgenic mice were equally divided into a CMTM2 + CP and a CMTM2 + NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT + CP and a WT + NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and motility by light microscopy and detection of the expression of StAR by Western blot.

RESULTSThe levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 + CP group as compared with the CMTM2 + NS group ([42.98 +/- 3.25] nmol/L vs [46.74 +/- 3.38] nmol/L, [16.89 +/- 1.17 ] x 10(6)/ml vs [24.68 +/- 0.95 ] x 10(6)/ml, [72.75 +/- 1.25]% vs [85.14 +/- 1.12]%, P < 0.05), but remarkably less than in the WT + CP group ([37.97 +/- 4.17] nmol/L, [12.75 +/- 1.02] x 10(6)/ml, [50.52 +/- 1.37] %) (P < 0.05). However, the expression of StAR was significantly higher in the CMTM2 + CP than in the WT + CP group (1.16 +/- 0.07 vs 0.69 +/- 0.08, P < 0.05).

CONCLUSIONCMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of StAR, and hence plays a protective role in the reproductive system.

Animals ; Cyclophosphamide ; toxicity ; MARVEL Domain-Containing Proteins ; genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Repressor Proteins ; genetics ; Sperm Count ; Sperm Motility ; Testis ; drug effects ; metabolism

BACKGROUNDCKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) located at 3p22.3, is a frequent deletion site and a tumor suppressor gene (TSG) locus in many cancer, which suggests CMTM7 may be a potential TSG. The aim of this study was to investigate the correlations of CMTM7 expression and survival rate in patients with non-smallcell lung cancer (NSCLC).

METHODSSurgical specimens of 180 cases with pathologically confirmed NSCLC were grouped into 18 tissue microarray slides. CMTM7 expression in these specimens were detected by immunohistochemistry staining and representative cases were confirmed by Western blotting. Univariate and multivariate analyses were performed to identify the association of CMTM7 expression with pathological features and survival of patients with NSCLC.

RESULTSA total of 78.9% of the 180 patients had variations of CMTM7 protein expression, either up-regulated or down-regulated. Univariate analysis showed that the patients' survival rate after surgery was highly correlated with CMTM7 expression (P = 0.0091). In addition, prognostic factors were examined by multivariate Cox regression analysis, and results suggested that CMTM7 expression was a unique prognostic factor in NSCLC survival.

CONCLUSIONSThe CMTM7 expression may be related to survival of patients with NSCLC and a unique prognostic factor. CMTM7 may play an important role in NSCLC development.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; chemistry ; mortality ; pathology ; Chemokines ; analysis ; genetics ; physiology ; Female ; Humans ; Lung Neoplasms ; chemistry ; mortality ; pathology ; MARVEL Domain-Containing Proteins ; analysis ; genetics ; physiology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Tissue Array Analysis ; Tumor Suppressor Proteins ; analysis ; genetics ; physiology

OBJECTIVETo investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism.

METHODSWe established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry.

RESULTSThe tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group.

CONCLUSIONCMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Chemokines ; genetics ; pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; pharmacology ; Male ; Mice ; Mice, Nude ; NF-kappa B ; metabolism ; Prostatic Neoplasms ; metabolism ; Tumor Suppressor Proteins ; genetics ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo establish a transgenic mouse model systemically expressing the CMTM2 gene and study the effect of the CMTM2 expression on the reproductive system of mice in vivo.

METHODSTransgenic mice were generated by microinjection of pRevTRE-CMTM2 and the genotype was detected by PCR. The expression of CMTM2 was determined by RT-PCR, Western blot and immunohistochemistry, and the serum testosterone level was measured by radioimmunoassay.

RESULTSThe CMTM2 gene was highly expressed in the testis of the transgenic mouse models and in their offspring as well. The level of serum testosterone was significantly increased in the transgenic models as compared with the wild-type mice ([46.04 +/- 3.72] vs [42.43 +/- 3.80] nmol/L, P < 0.05).

CONCLUSIONThe transgenic mouse model was established successfully, which could highly express the CMTM2 gene. It is indicated that CMTM2 may influence steroidogenesis and testosterone secretion in transgenic mice.

Animals ; Genotype ; MARVEL Domain-Containing Proteins ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Transgenic ; Testosterone ; blood

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.
Chemokines ; genetics ; metabolism ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; Signal Transduction ; Tumor Suppressor Proteins ; genetics ; metabolism

BACKGROUNDThe CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated.

METHODSThe effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-κB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation.

RESULTSThe results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription. CMTM2 exerted a suppressive action on both full-length HIV-1 provirus and HIV-1 LTR-directed transcription. Transcription factor assays showed that CMTM2 selectively inhibited basal AP-1 and CREB activity. Co-expression of HIV-1 Tat, a potent AP-1 and CREB activator, can not reverse CMTM2-mediated AP-1 and CREB inhibition, suggesting a potent and specific effect of CMTM2 on negatively regulating these two signaling pathways.

CONCLUSIONIntracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. Exploring the mechanisms further may lead to new ways to control HIV-1 replication.

Chemokines ; physiology ; Cyclic AMP Response Element-Binding Protein ; antagonists & inhibitors ; HIV Long Terminal Repeat ; HIV-1 ; genetics ; Humans ; Intracellular Space ; metabolism ; Jurkat Cells ; MARVEL Domain-Containing Proteins ; Tetradecanoylphorbol Acetate ; pharmacology ; Transcription Factor AP-1 ; antagonists & inhibitors ; Transcription, Genetic ; U937 Cells