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BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Tamara Babic ◽  
Sandra Dragicevic ◽  
Marko Miladinov ◽  
Zoran Krivokapic ◽  
Aleksandra Nikolic

Abstract Background Transcripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4–201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods Relative abundance of SMAD4–201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results The relative abundance of SMAD4–201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4–201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4–202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4–201 and SMAD4–202. Conclusion The expression profile of SMAD4–201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.

2022 ◽  
Vol 22 (1) ◽  
Dongxue Zhang ◽  
Wenyan Liu ◽  
Li Peng ◽  
Haiyan Wang ◽  
Mei Lin ◽  

Abstract Background To investigate the difference in the structural composition of salivary flora between chronic periodontitis patients with and without diabetic nephropathy (DN). Methods Thirty salivary samples of 15 chronic periodontitis patients with DN (DN group) and 15 chronic periodontitis patients with diabetes but without DN (DM group) were subjected to pyrosequencing of polymerase chain reaction-amplified 16 s ribosomal RNA genes. After diversity testing, the differential flora were analyzed. The sequencing results were compared with GenBank database to determine the type of differential flora using species composition analysis, hierarchical cluster analysis, principal co-ordinate analysis, and species difference analysis. Results There were significant between-group differences with respect to Gemella, Selenomonas spp, Lactobacillales_unclassified, Bacteria-unclassified and Abiotrophia (p < 0.05). Compared with DM group, the relative abundance of Selenomonas spp. in DN group was significantly higher; the area under the receiver operating characteristic curve of Selenomonas spp. was 0.713 (P < 0.05). Multi-level biological identification and feature maps indicated that Selenomonas spp. might be used as a potential biomarker for DN patients. On binary logistic regression analysis, increase of Selenomonas spp. was related with DN. Conclusions We found significant between-group differences in the structural composition of oral flora. The increase in the relative abundance of Selenomonas spp. may be associated with DN in patients with chronic periodontitis.

2022 ◽  
Vol 22 (1) ◽  
Zijian Ma ◽  
Ganyi Chen ◽  
Yiqian Chen ◽  
Zizhang Guo ◽  
Hao Chai ◽  

Abstract Background Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear. Methods miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA. Result In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3′-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region. Conclusions Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.

2022 ◽  
Vol 23 (1) ◽  
Thomas H. Jonkman ◽  
Koen F. Dekkers ◽  
Roderick C. Slieker ◽  
Crystal D. Grant ◽  
M. Arfan Ikram ◽  

Abstract Background Epigenetic clocks use DNA methylation (DNAm) levels of specific sets of CpG dinucleotides to accurately predict individual chronological age. A popular application of these clocks is to explore whether the deviation of predicted age from chronological age is associated with disease phenotypes, where this deviation is interpreted as a potential biomarker of biological age. This wide application, however, contrasts with the limited insight in the processes that may drive the running of epigenetic clocks. Results We perform a functional genomics analysis on four epigenetic clocks, including Hannum’s blood predictor and Horvath’s multi-tissue predictor, using blood DNA methylome and transcriptome data from 3132 individuals. The four clocks result in similar predictions of individual chronological age, and their constituting CpGs are correlated in DNAm level and are enriched for similar histone modifications and chromatin states. Interestingly, DNAm levels of CpGs from the clocks are commonly associated with gene expression in trans. The gene sets involved are highly overlapping and enriched for T cell processes. Further analysis of the transcriptome and methylome of sorted blood cell types identifies differences in DNAm between naive and activated T and NK cells as a probable contributor to the clocks. Indeed, within the same donor, the four epigenetic clocks predict naive cells to be up to 40 years younger than activated cells. Conclusions The ability of epigenetic clocks to predict chronological age involves their ability to detect changes in proportions of naive and activated immune blood cells, an established feature of immuno-senescence. This finding may contribute to the interpretation of associations between clock-derived measures and age-related health outcomes.

2022 ◽  
Vol 8 ◽  
Layla Honorato ◽  
Steven S. Witkin ◽  
Maria Cássia Mendes-Correa ◽  
Ana Luiza Castro Conde Toscano ◽  
Iara Moreno Linhares ◽  

IntroductionTorque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer.MethodsSaliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review.ResultsTTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p &lt; 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p &lt; 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p &lt; 0.0001).ConclusionThe TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.

2022 ◽  
Vol 15 (1) ◽  
Lili Zhong ◽  
Xiumin Liu ◽  
Lixing Wang ◽  
Yu Liu ◽  
Duohan Zhang ◽  

Abstract Objective High-grade serous ovarian cancer (HGSOC) is an aggressive gynaecological malignancy and associated with poor prognosis. Here we examined the effects of miR-625-3p on proliferation, treatment, migration and invasion in HGSOC. Methods The proliferation of HGSOC cells was evaluated by MTT assay. Transwell assay was performed to examine migration and matrigel assay were used to assess invasion. The effect of miR-625-3p on cisplatin-induced apoptosis was investigated by Caspase-Glo3/7 assay. The dual-luciferase reporter assay was carried out to confirm the potential binding site. Results Overexpression of miR-625-3p promoted proliferation, and increased migration and invasion in HGSOC cells. MiR-625-3p significantly inhibited cisplatin sensitivity in HGSOC cells. Meanwhile, miR-625-3p decreased cisplatin-induced apoptosis by regulation of BAX and Bcl-2 expression. Furthermore, aberrant expression of miR-625-3p changed PTEN expression by directly binding to 3’UTR of PTEN. Further study showed miR-625-3p expression was higher in human HGSOC tissue than normal ovarian tissues and associated with higher clinical stage. Conclusions miR-625-3p promotes HGSOC growth, involves chemotherapy resistance and might serve as a potential biomarker to predict chemotherapy response and prognosis in HGSOC.

2022 ◽  
Vol 8 ◽  
Chiao-Yi Lin ◽  
Wen-Ting Tseng ◽  
Yao-Yin Chang ◽  
Mong-Hsun Tsai ◽  
Eric Y. Chuang ◽  

Background: Breast cancer is the most common malignancy and a leading cause of death among women. The majority of patients require surgery, and retrospective studies have revealed an association between anaesthetic techniques during surgery and clinical outcomes. Local anaesthetics (LAs) influence carcinogenesis by interacting with non-coding RNAs (ncRNAs). However, the detailed mechanisms underlying the association between LAs and ncRNAs remain unclear.Methods: In this study, the effects of two commonly used LAs, lidocaine and bupivacaine, on the malignancy of MCF-7 breast cancer cells were investigated. The expression profiles of the microRNAs (miRNAs) that responded to treatment with LAs were determined through next-generation sequencing.Results: Data from the functional assay revealed that the LAs suppressed the proliferation of MCF-7 cells. The result of next-generation sequencing revealed that 131 miRNAs were upregulated, following treatment with the LAs. Validation using polymerase chain reaction (PCR) identified miR-187-5p as a potential biomarker, and it was selected for further analyses. Prediction with bioinformatics tools and luciferase reporter assays revealed that MYB is a direct target gene of miR-187-5p. Based on the hypothesis that lncRNAs acts as miRNA sponges, the target lncRNA, DANCR, of miR-187-5p was predicted using DIANA-LncBase v2 and validated using luciferase reporter assays. In addition, the reciprocal suppressive effect between DANCR and miR-187-5p was determined.Conclusions: This study suggests that one of the anti-tumour mechanisms of lidocaine and bupivacaine is mediated through the DANCR-miR-187-5p-MYB axis. This may provide a novel molecular mechanism of tumour suppression in breast cancer.

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Ruoyu Chen ◽  
Anyi Liang ◽  
Jie Yao ◽  
Zicheng Wang ◽  
Yesheng Chen ◽  

Background and Objective. To correlate optical coherence tomography angiography (OCTA) characteristics of diabetic microaneurysms (MAs) with leakage status on fluorescein angiography (FA). Patients and Methods. 167 MAs from 39 diabetic eyes were analyzed using OCTA and FA simultaneously. The characteristics of MAs on OCTA en face, OCT en face, and OCT B-scan with flow overlay were evaluated and correlated with fluorescein leakage status. Results. Thirty-six, fifty-two, and seventy-nine MAs showed no, mild, and severe leakage on FA, respectively. Most MAs (61.7%) were centered in the inner nuclear layer. Cystoid spaces were observed adjacent to 60 (35.9%) MAs. MAs with severe leakage had a statistically higher flow proportion compared to MAs with no or mild leakage (both P < 0.001 ). Only 112 MAs (67.1%) were visualized in the OCTA en face images, while 165 MAs (98.8%) could be visualized in the OCT en face images. The location of MAs did not associate significantly with FA leakage status. The presence of nearby cystoid spaces and higher flow proportion by OCT B-scan with flow overlay correlated significantly with FA leakage status. Conclusion. The flow proportion of MAs observed on OCT B-scans with flow overlay might be a potential biomarker to identify leaking MAs. A combination of OCT B-scan, OCT en face, and OCTA en face images increased the detection rate of diabetic MAs in a noninvasive way.

2022 ◽  
Vol 11 ◽  
Wanrui Lv ◽  
Ke Cheng ◽  
Xiaofen Li ◽  
Lusi Feng ◽  
Hancong Li ◽  

Some pertinent studies have demonstrated that Epstein–Barr virus-associated gastric cancer (EBVaGC) patients showed a favorable clinical outcome to immunotherapy and Epstein–Barr virus (EBV)-positive status might be a potential biomarker for immunotherapy in gastric cancer (GC). However, knowledge of given exposure to EBVaGC to the first-line immunotherapy is largely inadequate. Moreover, whether camrelizumab can be as effective as other PD-1 inhibitors in the treatment of advanced EBVaGC has not been reported. We report a case of advanced EBVaGC patient with a positive expression of PD-L1, enriched PD-L1+CD68+macrophages, and high TMB who had a long-term partial response and manageable toxicity to the combined approach of camrelizumab (a novel PD-1 inhibitor) and oxaliplatin plus oral S-1 (SOX). As the first-line treatment of advanced EBVaGC patients, camrelizumab combined with SOX regimen may provide a novel combined approach with favorable response and manageable safety. Combination of multiple biomarkers could have a higher effective predictive capacity to immunotherapy. Integrated treatment (chemo-immunotherapy and radiotherapy) might be the optimal strategy for patients with oligometastasis. It deserves prospective research to further validate the efficacy.

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 189
Janina Świderska ◽  
Mateusz Kozłowski ◽  
Katarzyna Nowak ◽  
Małgorzata Rychlicka ◽  
Dorota Branecka-Woźniak ◽  

It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11–1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14–1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91–1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01–1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10–1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19–1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer.

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