Journal of Cellular and Molecular Medicine最新文献

{"title":"Analysis of MUC6 polymorphisms on the clinicopathologic characteristics of Asian patients with oral squamous cell carcinoma","authors":"Chun-Hung Hua,&nbsp;Chun-Yi Chuang,&nbsp;Yi-Chung Chien,&nbsp;Chun-Wen Su,&nbsp;Shuo-Chueh Chen,&nbsp;Liang-Chih Liu,&nbsp;Shun-Fa Yang,&nbsp;Yung-Luen Yu","doi":"10.1111/jcmm.17886","DOIUrl":"10.1111/jcmm.17886","url":null,"abstract":"<p>Head and neck squamous cell carcinomas (HNSCCs) are generally associated with tobacco consumption, alcohol abuse or both. Mucins (MUCs) are high-molecular-weight glycoproteins produced by many epithelial tissues. Many studies have indicated that MUCs play an important role in cancer metastasis. <i>MUC6</i> expression has been observed in gastric and oncocytic phenotypes and plays an important role during cancer progression. We found that levels of <i>MUC6</i> are lower in Asian HNCC patients and affect the disease-free survival of HNCC patients. Next, we investigated the combined effect of <i>MUC6</i> polymorphisms and exposure to environmental carcinogens on the susceptibility to and clinicopathological characteristics of HNCC. Three single-nucleotide polymorphisms (SNPs) of <i>MUC6</i> (rs7481521, rs6597947 and rs61869016) were analysed using real-time PCR. After adjusting for other co-variants, we found that carrying a CC genotype at <i>MUC6</i> rs6597947 led to a lower risk of developing oral squamous cell carcinoma (OSCC) than wild-type carriers among non-betel-quid chewers. Moreover, male oral cancer patients who carried the AA + CC genotype at <i>MUC6</i> rs6597947 had a lower risk of lymph node metastasis than other genotypes, suggesting a significant functional compromise and decompensated disease. Therefore, our findings suggest that genetic variations in <i>MUC6</i> may correlate to OSCC and indicate the progression in OSCC patients.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2594-2602"},"PeriodicalIF":5.3,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer","authors":"He Zhang,&nbsp;Jianfei Tian,&nbsp;Sixin Ren,&nbsp;Baoai Han,&nbsp;Ruinan Tian,&nbsp;Xiaoyan Zuo,&nbsp;Hui Liu,&nbsp;Zhiyong Wang,&nbsp;Yanfen Cui,&nbsp;Liming Liu,&nbsp;Hui Guo,&nbsp;Fei Zhang,&nbsp;Ruifang Niu","doi":"10.1111/jcmm.17849","DOIUrl":"10.1111/jcmm.17849","url":null,"abstract":"<p>Splicing factors (SFs) are proteins that control the alternative splicing (AS) of RNAs, which have been recognized as new cancer hallmarks. Their dysregulation has been found to be involved in many biological processes of cancer, such as carcinogenesis, proliferation, metastasis and senescence. Dysregulation of SFs has been demonstrated to contribute to the progression of prostate cancer (PCa). However, a comprehensive analysis of the prognosis value of SFs in PCa is limited. In this work, we systematically analysed 393 SFs to deeply characterize the expression patterns, clinical relevance and biological functions of SFs in PCa. We identified 53 survival-related SFs that can stratify PCa into two de nove molecular subtypes with distinct mRNA expression and AS-event expression patterns and displayed significant differences in pathway activity and clinical outcomes. An SF-based classifier was established using LASSO-COX regression with six key SFs (BCAS1, LSM3, DHX16, NOVA2, RBM47 and SNRPN), which showed promising prognosis-prediction performance with a receiver operating characteristic (ROC) &gt;0.700 in both the training and testing datasets, as well as in three external PCa cohorts (DKFZ, GSE70769 and GSE21035). CRISPR/CAS9 screening data and cell-level functional analysis suggested that LSM3 and DHX16 are essential factors for the proliferation and cell cycle progression in PCa cells. This study proposes that SFs and AS events are potential multidimensional biomarkers for the diagnosis, prognosis and treatment of PCa.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2684-2700"},"PeriodicalIF":5.3,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-3133 inhibits gastrointestinal cancer progression through activation of Hippo and p53 signalling pathways via multi-targets","authors":"Ling Zhou,&nbsp;Hui Guo,&nbsp;Quan Liao,&nbsp;Jianping Zou,&nbsp;Yi Le,&nbsp;Ziling Fang,&nbsp;Jianping Xiong,&nbsp;Shanshan Huang,&nbsp;Jun Deng,&nbsp;Xiaojun Xiang","doi":"10.1111/jcmm.17880","DOIUrl":"10.1111/jcmm.17880","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant cell growth and chemoresistance, the main obstacles in treating gastrointestinal cancer (GIC), rely on the Hippo and p53 signalling pathways. However, the upstream regulatory mechanisms of these pathways remain complex and poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemistry (IHC), western blot and RT-qPCR were used to analyse the expression of RNF146, miR-3133 and key components of Hippo and p53 pathway. CCK-8, colony formation, drug sensitivity assays and murine xenograft models were used to investigate the effect of RNF146 and miR-3133 in GIC. Further exploration of the upstream regulatory mechanism was performed using bioinformatics analysis, dual-luciferase reporter gene, immunoprecipitation assays and bisulfite sequencing PCR (BSP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clinical samples, in vitro and in vivo experiments demonstrated that RNF146 exerts oncogenic effects in GIC by regulating the Hippo pathway. Bioinformatics analysis identified a novel miRNA, miR-3133, as an upstream regulatory factor of RNF146. fluorescence in situ hybridization and RT-qPCR assays revealed that miR-3133 was less expressed in gastrointestinal tumour tissues and was associated with adverse pathological features. Functional assays and animal models showed that miR-3133 promoted the proliferation and chemotherapy sensitivity of GIC cells. miR-3133 affected YAP1 protein expression by targeting RNF146, AGK and CUL4A, thus activating the Hippo pathway. miR-3133 inhibited p53 protein degradation and extended p53's half-life by targeting USP15, SPIN1. BSP experiments confirmed that miR-3133 promoter methylation is an important reason for its low expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>miR-3133 inhibits GIC progression by activating the Hippo and p53 signalling pathways via multi-targets, including RNF146, thereby providing prognostic factors and valuable potential therapeutic targets for GIC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3090-3106"},"PeriodicalIF":5.3,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17880","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPI1 involvement in malignant melanoma pathogenesis by regulation of HK2 through the AKT1/mTOR pathway","authors":"Chunlei Liu,&nbsp;Xiujuan Qiu,&nbsp;Jun Gao,&nbsp;Zhifan Gong,&nbsp;Xiaogang Zhou,&nbsp;Haichao Luo,&nbsp;Xuerui Geng","doi":"10.1111/jcmm.17844","DOIUrl":"10.1111/jcmm.17844","url":null,"abstract":"<p>Spi-1 proto-oncogene (SPI1) plays a vital role in carcinogenesis. Our work aimed to investigate the potential regulatory mechanism of SPI1 in melanoma. The mRNA and protein levels were measured via qRT–PCR and Western blotting. Cell viability was assessed by CCK-8 assay. The target relationship between SPI1 and hexokinase 2 (HK2) was determined using dual-luciferase reporter detection. ChIP was conducted to confirm the targeted relationship between SPI1 and the HK2 promoter. Immunohistochemistry analysis was conducted to measure the positive cell number of SPI1 and HK2 in melanoma tissues. The cell migration abilities were determined using a wound healing assay. Glucose consumption, pyruvate dehydrogenase activity, lactate production and ATP levels were measured to assess glycolysis. SPI1 transcription in melanoma cells and tissues was dramatically higher than that in adjacent normal tissues and epidermal melanocyte HEMa-LP, respectively. Knockdown of SPI1 restrained cell viability, metastasis and glycolysis in melanoma cells. SPI1 directly targeted HK2, and knockdown of SPI1 repressed HK2 expression. Overexpression of HK2 weakened the inhibitory effects of SPI1 knockdown on the viability, metastasis and glycolysis of melanoma cells. The serine–threonine kinase 1 (AKT1)/mammalian target of rapamycin (mTOR) axis is involved in melanoma progression. SPI1 knockdown restrained melanoma cell proliferation, metastasis and glycolysis by regulating the AKT1/mTOR pathway.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2675-2683"},"PeriodicalIF":5.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hirudin inhibits glioma growth through mTOR-regulated autophagy","authors":"Ying Ma,&nbsp;Senbin Wu,&nbsp;Fanyi Zhao,&nbsp;Huifeng Li,&nbsp;Qiaohong Li,&nbsp;Jingzhi Zhang,&nbsp;Hua Li,&nbsp;Zhongmin Yuan","doi":"10.1111/jcmm.17851","DOIUrl":"10.1111/jcmm.17851","url":null,"abstract":"<p>Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose- and time-dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3-II but not Caspase-3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell-derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3-II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin-induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2701-2713"},"PeriodicalIF":5.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia","authors":"Feng Wan,&nbsp;Lan Yu,&nbsp;Xiaowei Qu,&nbsp;Yanqing Xia,&nbsp;Ke Feng,&nbsp;Lei Zhang,&nbsp;Na Zhang,&nbsp;Guihua Zhao,&nbsp;Cuilian Zhang,&nbsp;Haibin Guo","doi":"10.1111/jcmm.17881","DOIUrl":"10.1111/jcmm.17881","url":null,"abstract":"<p>Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. <i>DNAAF3</i> is identified as a novel gene associated with PCD and different mutations in <i>DNAAF3</i> results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in <i>DNAAF3</i>(c.551T&gt;A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the <i>DNAAF3</i> had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within <i>DNAAF3</i> also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with <i>DNAAF3</i> mutations but also expands the spectrum of <i>DNAAF3</i> mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3107-3116"},"PeriodicalIF":5.3,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells","authors":"Mahtab Shahriari Felordi,&nbsp;Mehdi Alikhani,&nbsp;Zahra Farzaneh,&nbsp;Mahmoud Alipour Choshali,&nbsp;Marzieh Ebrahimi,&nbsp;Hamidreza Aboulkheyr Es,&nbsp;Abbas Piryaei,&nbsp;Mustapha Najimi,&nbsp;Massoud Vosough","doi":"10.1111/jcmm.17873","DOIUrl":"10.1111/jcmm.17873","url":null,"abstract":"<p>Anti-cancer properties of (-)-epigallocatechin-3-gallate (EGCG) are mediated via apoptosis induction, as well as inhibition of cell proliferation and histone deacetylase. Accumulation of stabilized cellular FLICE-inhibitory protein (c-FLIP)/Ku70 complex in the cytoplasm inhibits apoptosis through interruption of extrinsic apoptosis pathway. In this study, we evaluated the anti-cancer role of EGCG in gastric cancer (GC) cells through dissociation of c-FLIP/Ku70 complex. MKN-45 cells were treated with EGCG or its antagonist MG149 for 24 h. Apoptosis was evaluated by flow cytometry and quantitative RT-PCR. Protein expression of c-FLIP and Ku70 was analysed using western blot and immunofluorescence. Dissociation of c-FLIP/Ku70 complex as well as Ku70 translocation were studied by sub-cellular fractionation and co-immunoprecipitation. EGCG induced apoptosis in MKN-45 cells with substantial up-regulation of <i>P53</i> and <i>P21</i>, down-regulation of <i>c-Myc</i> and <i>Cyclin D1</i> as well as cell cycle arrest in S and G2/M check points. Moreover, EGCG treatment suppressed the expression of c-FLIP and Ku70, decreased their interaction while increasing the Ku70 nuclear content. By dissociating the c-FLIP/Ku70 complex, EGCG could be an alternative component to the conventional HDAC inhibitors in order to induce apoptosis in GC cells. Thus, its combination with other cancer therapy protocols could result in a better therapeutic outcome.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2572-2582"},"PeriodicalIF":5.3,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17873","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of extracellular vesicles isolated from hydatid cyst fluid and evaluation of immunomodulatory effects on human monocytes","authors":"Mojdeh Khosravi,&nbsp;Hanieh Mohammad Rahimi,&nbsp;Abdoreza Nazari,&nbsp;Kaveh Baghaei,&nbsp;Hamid Asadzadeh Aghdaei,&nbsp;Shabnam Shahrokh,&nbsp;Meysam Sharifdini,&nbsp;Ana Claudia Torrecilhas,&nbsp;Fatemeh Mehryab,&nbsp;Hamed Mirjalali,&nbsp;Faezeh Shekari,&nbsp;Mohammad Reza Zali","doi":"10.1111/jcmm.17894","DOIUrl":"10.1111/jcmm.17894","url":null,"abstract":"<p>Hydatidosis is a disease caused by the larval stage of <i>Echinococcus granulosus</i>, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP-1) was evaluated. The effects of EVs on the expression levels of pro- and anti-inflammatory cytokines were investigated using quantitative real-time PCR (RT-PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL-10 was evaluated in supernatant of THP-1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro-inflammatory cytokine genes (<i>IL1Β</i>, <i>IL15</i> and <i>IL8</i>) were upregulated, while after 24 h, the expression levels of pro-inflammatory cytokines were decreased and <i>IL13</i> gene expression showed upregulation. A statistically significant increase was seen in the levels of IL-10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time-dependent anti-inflammatory effects in our study suggest that HC may modulate the immune responses via EVs.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2614-2625"},"PeriodicalIF":5.3,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hairy cell leukaemia with unusual BRAF mutations","authors":"Elsa Maitre,&nbsp;Margaret Macro,&nbsp;Xavier Troussard","doi":"10.1111/jcmm.17890","DOIUrl":"10.1111/jcmm.17890","url":null,"abstract":"<p>Hairy cell leukaemia (HCL) diagnosis is based on the morphologic detection of circulating abnormal hairy cells in the peripheral blood and/or bone marrow, an HCL immunological score of 3 or 4 based on the expression of the CD11c, CD25, CD103 and CD123 and also the presence of a <i>BRAF V600E</i> activating mutation in the B-raf proto-oncogene (BRAF gene) (7q34). When using new generation sequencing of 21 targeted genes in 124 HCL patients, we identified a cohort of 6/124 (2%) patients with unusual <i>BRAF</i> mutations: two patients presented non-V600 mutations (BRAF F595L, BRAF W604L respectively) and four other patients silent BRAF mutations. When using droplet digital PCR (ddPCR) three of the four patients with concomitant <i>BRAF V600E</i> and silent mutation were negative. The respective role of these mutations in the occurrence of HCL or its progression remains to be clarified, but <i>BRAF</i> sequencing is necessary in case of negative <i>BRAF V600E</i> by ddPCR.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2626-2630"},"PeriodicalIF":5.3,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants of dipeptidyl peptidase IV are linked to the clinicopathologic development of prostate cancer","authors":"Yu-Ching Wen,&nbsp;Chia-Yen Lin,&nbsp;Chi-Hao Hsiao,&nbsp;Shian-Shiang Wang,&nbsp;Hsiang-Ching Huang,&nbsp;Yung-Wei Lin,&nbsp;Kuo-Hao Ho,&nbsp;Lun-Ching Chang,&nbsp;Shun-Fa Yang,&nbsp;Ming-Hsien Chien","doi":"10.1111/jcmm.17845","DOIUrl":"10.1111/jcmm.17845","url":null,"abstract":"<p>CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell-surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence indicating a tumour-promoting or -suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case–control study to evaluate whether single-nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062–2.659, <i>p</i> = 0.025; AOR: 1.693, 95% CI: 1.092–2.624, <i>p</i> = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression-free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 17","pages":"2507-2516"},"PeriodicalIF":5.3,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}