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The extracellular secretion of miR-1825 wrapped by exosomes increases CLEC5A expression:A potential oncogenic mechanism in ovarian cancer

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BIOCELL 2023年第5期47卷 1039-1050页

作者： QIAOLING WU zhaolei cui HONGMEI XIA SHAN JIANG JING BAI ZHUO SHAO YANG SUN Department of Gynecology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Gynecology Shengli Clinical Medical College of Fujian Medical UniversityFuzhouChina Laboratory of Biochemistry and Molecular Biology Research Department of Clinical LaboratoryClinical Oncology School of FujianMedical UniversityFujian Cancer HospitalFuzhouChina Geneplus-Beijing Institute BeijingChina

Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths *** miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further ***:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)*** genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried *** ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier *** CLEC5A expression pattern in OC was validated using *** CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO ***,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also ***:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor *** CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in *** the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was ***:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.

关键词： Exosome MicroRNA-1825 C-type lectin domain family 5 member A PI3K-Akt pathway Tumor immune microenvironment

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Performance of A PLK1-Based Immune Risk Model for Prognosis and Response Prediction of Breast Cancer

Performance of A PLK1-Based Immune Risk Model for Prognosis ...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:Polo-like kinase 1(PLK1) belongs to a family of serine/threonine-protein kinases and acts as a powerful oncogene in tumor occurrence and *** aimed to assess potential correlations between PLK1 expression and immune infiltration in BRCA and construct a PLK1-based immune risk model applicable for prognosis and response ***:We collected gene expression data of PLK1 in BRCA patients from *** of PLK1 expression with immune cell infiltration and immunomodulators were critically analyzed.A prognostic risk model based on seven genes for PLK1-related immunomodulators was established,and a nomogram was depicted for survival ***:PLK1 expression was significantly associated with BRCA prognosis,clinical stage progression,and tumor *** PLK1 gene was significantly enriched in T cell and B cell receptors,and molecules of the chemokine signaling ***,PLK1expression was positively correlated with the degree of activated CD8+T cell,regulatory T cell(Tregs),and negatively correlated with M2 macrophage *** seven-gene-based risk model could serve as an independent prognostic factor of *** risk model was markedly correlated with PD-1/PD-L1(both P<0.001) immune checkpoints expression and tumor mutation burden(TMB).Patients at high and low risk of BRCA identified by the risk model revealed different responses to anti-PD-1 and/or anti-CTLA4therapy,as well as common chemotherapy drugs like cisplatin,paclitaxel,and ***:This PLK1-based immune risk model can effectively predict the prognosis and tumor progression of BRCA,identify gene mutations,and assess patient benefits from immunotherapy and chemotherapy regimens.

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Lactate Dehydrogenase C4 is associated with breast cancer prognosis and affects cancer cell proliferation and invasion

Lactate Dehydrogenase C4 is associated with breast cancer pr...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:Human lactate dehydrogenase C4(LDH-C4) is a known cancer/testis antigen(CTA).Nevertheless,its clinical effects and molecular role remains unclear in breast cancer(BC).Methods:Expression of LDH-C4 in BC tissue,paired adjacent normal tissue,and cell lines were quantified by qRT-PCR,western blotting and ***,we assessed the clinical and prognostic significance of LDH-C4 in BC by Kaplan-Meier *** proliferation,migration and invasion,and cell apoptosis were measured by means of a cell counting kit-8,clone forming,Transwell assay,and TUMMEL,*** an Results:Expression levels of LDH-C4 were markedly upregualted in BC cells and tumor tissues but not expressed in normal BC ***,survival showed that high LDH-C4expression conferred reduced survival rates(P<0.05).Functional analyses revealed that LDH-C4 overexpression and down-regulation attenuated cell proliferation,invasion,and migration as well as energy metabolism in BC ***-C4 could affect m TOR ***:Expression of LDH-C4 in BC may serve as a potential indicator for poor ***-C4 displays tumor suppressive behavior,warranting future investigations into its therapeutic potential in the treatment of BC.

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Endogenous SARI induced cell apoptosis in nasopharyngeal carcinoma by targeting the intrinsic apoptotic pathway

Endogenous SARI induced cell apoptosis in nasopharyngeal car...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

The SARI(suppressor of AP-1,regulated by IFN) gene,also named as BATF2,is associated with the risk of several kinds of cancers,and loss of SARI expression is frequently detected in aggressive and metastatic ***,the functional of SARI in nasopharyngeal carcinoma(NPC) remains *** this study,we discovered that knock-down of SARI expression suppressed cell growth and colony formation,inhibited invasion,promoted apoptosis,and induced G0/G1 and G2/M arrest in human CNE2 nasopharyngeal carcinoma *** note,SARI restoration could trigger the mitochondrial pathway in CNE2 *** data provide evidence that SARI exerts a role as a tumor suppressor gene in leukemia,possibly by inhibiting proliferation and promoting apoptosis via the mitochondrial pathway.

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Diagnostic potential for circular RNAs in gastric carcinoma:A meta-analysis

Diagnostic potential for circular RNAs in gastric carcinoma:...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Background:Circular RNAs(circRNAs) are potential,novel biomarkers for the early diagnosis of gastric ***,a meta-analysis was conducted to assess the diagnostic potential for circRNAs in gastric ***:Online databases were searched for eligible *** quality was judged using the Quality Assessment for Studies of Diagnostic Accuracy(QUADAS) checklist-II ***12.0 and Meta-Disc 1.4 software were used for statistical ***:Twelve studies consisting of 1278 patients and 1250 paired controls were considered for *** pooled sensitivity and specificity of circRNAs for gastric carcinoma was compared to normal controls and found to be 0.68(95%CI:0.66-0.71) and 0.70(95%CI:0.68-0.73),respectively.A corresponding area under the receiver operating characteristic curve of 0.78 was ***,stratified analysis demonstrated an improved diagnostic value for circRNAs when tissue and plasma specimens were ***:This meta-analysis demonstrates that circRNAs are promising biomarkers for gastric carcinoma.

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Diagnostic and prognostic value of the cancer-testis antigen LDH-C4 in breast cancer

Diagnostic and prognostic value of the cancer-testis antigen...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:Lactate dehydrogenase C4(LDH-C4) is a cancer/testis antigen(CTA) that is expressed abnormally in certain malignant ***,the expression and clinical significance of LDH-C4 in breast cancer(BC) have not been ***:Quantitative reverse transcription-polymerase chain reaction(RT-PCR) was adopted to investigate the expression of LDHC m RNA in the serum or serum-derived exosomes of patients with *** expression of LDH-C4 protein in BC tissues was also evaluated by using high-throughput tissue microarray analysis and ***:The results showed that LDHC mRNA was highly expressed in the serum and serum-derived exosomes of BC *** area under the curve(AUC) of serum and exosome LDHC in distinguishing BC from healthy individuals was estimiated to be 0.9587and 0.9464,*** LDHC level in the serum-derived exosomes of patients with BC was significantly associated with tumor size and positively correlated with the expression of HER2 and Ki-67(all with p<0.05).Serum and exosome LDHC levels in BC patients were negatively correlated with medical treatment and positively correlated with *** analysis showed that LDH-C4 expression was negatively associated with BC ***:Serum and serum-derived exosome LDHC may be an effective indicator for diagnosis and therapeutic efficacy,as well as a predictor for the recurrence of ***-C4may be a biomarker to determine the prognosis of BC.

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ARA55 participates in TGFβ1-induced epithelial-mesenchymal transition in CNE2 nasopharyngeal carcinoma cells

ARA55 participates in TGFβ1-induced epithelial-mesenchymal ...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:ARA55(androgen receptor coactivator 55kDa protein) was first identified as a TGFβ1-inducible protein and function as a molecular scaffold in coordinating protein-protein ***,we focused on validating the functional role of ARA55 in TGFβ1-induced epithelial-mesenchymal transition(EMT) in human CNE2 nasopharyngeal carcinoma ***:Expression of ARA55 in the CNE2 cells was stimulated by TGFβ1(5ng/ml),and a commercial RNA interference plasmid(siRNA-ARA55) was utilized to silence ARA55expression in response to TGFβ1 ***:Our results manifested that forced expression of ARA55 enhances growth as well as migration and invasion of the CEN2 *** contrast,cells depleted of ARA55 resulted in suppressed cell proliferation and metastasis capability,along with a down-regulation of N-cadherin and up-regulation of *** co-immunoprecipitation analysis exhibited that induced ARA55 yields a direct physical interaction with Smad7 in TGFβ***:Our data demonstrate that ARA55 exerts a causative role and functions as a critical regulator in TGFβ1-mediated EMT in CNE2 nasopharyngeal carcinoma cells through binding with Smad7.

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Diagnostic and Prognostic Potential of Circulating and Tissue BATF2 in Nasopharyngeal Carcinoma

Diagnostic and Prognostic Potential of Circulating and Tissu...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:At present,there is still a lack of effective markers for early diagnosis and prognostic monitoring of nasopharyngeal carcinoma(NPC).A large number of studies have shown that the basic leucine zipper ATF-like transcription factor 2(BATF2) gene is closely related to the occurrence and development of a variety of malignant ***,the expression of BATF2 in NPC and its clinical significance is still ***:A high-throughput tissue microarray combined with immunohistochemistry(IHC) was used to detect the expression of BATF2 proteins in NPC tissues,and to explore its relationship with clinicopathological characteristics and the prognosis of ***,a quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to detect the expression of BATF2 mRNA in serum and serum-derived exosomes of NPC ***:The IHC showed that BATF2 was mainly localized to the nucleus of NPC tissue *** analysis showed that the NPC patients with a positive BATF2 expression enjoyed a longer duration of overall survival than those with a negative BATF2 *** positive expression rates of BATF2 mRNA in serum and serum exosomes of NPC patients were 51.47% and 48.52%,*** AUCs of NPC patients diagnosed by serum and exosomal BATF2 and healthy control groups were 0.9409 and 0.8983,*** BATF2 levels of serum and exosomes of NPC patients in the treatment group were higher than those in the initial group,but lower than those in the recurrence ***:BATF2 is expected to be a promising prognostic marker for ***2 in serum and serum exosomes can be used as an important biomarker for diagnosis,efficacy evaluation,and recurrence monitoring of NPC.

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Expression and Clinical Implications of Basic Leucine Zipper ATF-Like Transcription Factor 2 in Breast Cancer

Expression and Clinical Implications of Basic Leucine Zipper...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:Basic leucine zipper ATF-like transcription factor 2(BATF2) has been reported to participate in the occurrence and development of some *** little is known about its roles in breast cancer(BC).In this work,we aimed to explore the expression pattern and clinical implications of BATF2 in ***:We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using online *** external validations,BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemical(IHC) analysis,and BATF2 m RNA expression in serum and serum-derived exosomes of BC patients using ***:There were low-to-moderate levels of increases in BATF2 protein expressions in BC ***2 mRNA expression was negatively correlated with androgen receptor(AR) and positively correlated with BRCA2,Mki67,and TP53 *** analyses showed that triple-negative breast cancer(TNBC) patients with high BATF2 m RNA expressions had a longer overall survival(OS).Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%.The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00% and 41.67%,***,the AUCs of serum and exosomal BATF2 m RNA for BC diagnosis were 0.8929 and 0.8869,***:BC patients exhibit low-to-moderate increases in BATF2 m RNA expression levels in cancerous tissues,of which low BATF2 mRNA expression serves as an indicator of a poor TNBC *** high BATF2 protein expression can be a potential indicator of a better BC *** and exosomal BATF2 m RNA levels also serve as promising noninvasive biomarkers for BC diagnosis.

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Identification of Adriamycin Resistance Genes in Breast Cancer based on Microarray Data Analysis

Identification of Adriamycin Resistance Genes in Breast Canc...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： zhaolei cui Yan Chen Fujian Cancer Hospital

Objective:Breast cancer is a common malignant tumor with increasing incidence *** study aimed to investigate the molecular mechanisms of the adriamycin(ADR)resistance in breast ***:The GSE76540 dataset downloaded from the National Center for Biotechnology Information(NCBI) Gene Expression Omnibus(GEO) database was adopted for *** expressed genes(DEGs) in chemo-sensitive cases and chemo-resistant cases were identified using the GEO2R online tool *** analysis and KEGG enrichment analysis of DEGs were carried out by using the DAVID online *** protein-protein interaction(PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes(STRING) and visualized with Cytoscape *** impact of key tumor genes on the survival and prognosis were ***:A total of 1481 DEGs were excavated,including 549 up-regulated genes and 932down-regulated *** to the GO analysis,the DEGs were significantly enriched in:extracellular matrix organization,positive regulation of transcription from RNA polymerase II promoter,lung development,positive regulation of gene expression,axon quidance and so *** results of KEGG pathway enrichment analysis showed that the most enriched DEGs can be detected in:pathways in cancer,PI3K AKT signaling pathway,focal adhesion,ras signaling pathway and so *** the PPI network analysis,hub genes of CDH1,ESR1,SOX2,AR,GATA3,FOXA1,KRT19,CLDN7,AGR2,ESRP1,RAB25,CLDN4,IGF1R,CLDN3 and IRS1 were ***,there is a correlation filter out these hub genes in resistance of ***:Hub genes associated with ADR resistance were identified using bioinformatic *** results of this study may contribute to the development of targeted therapy for breast cancer.

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