scholarly journals The microRNA target site landscape is a novel molecular feature associating alternative polyadenylation with immune evasion activity in breast cancer

2020 ◽  
Author(s):  
Soyeon Kim ◽  
YuLong Bai ◽  
Zhenjiang Fan ◽  
Brenda Diergaarde ◽  
George C Tseng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mirna Target ◽  
Alternative Polyadenylation ◽  
Regulatory Elements ◽  
Target Site ◽  
Mirna Target Site ◽  
Breast Cancer Data ◽  
Microrna Target ◽  
Cancer Data ◽  
Target Sites

Abstract Alternative polyadenylation (APA) in breast tumor samples results in the removal/addition of cis-regulatory elements such as microRNA (miRNA) target sites in the 3′-untranslated region (3′-UTRs) of genes. Although previous computational APA studies focused on a subset of genes strongly affected by APA (APA genes), we identify miRNAs of which widespread APA events collectively increase or decrease the number of target sites [probabilistic inference of microRNA target site modification through APA (PRIMATA-APA)]. Using PRIMATA-APA on the cancer genome atlas (TCGA) breast cancer data, we found that the global APA events change the number of the target sites of particular microRNAs [target sites modified miRNA (tamoMiRNA)] enriched for cancer development and treatments. We also found that when knockdown (KD) of NUDT21 in HeLa cells induces a different set of widespread 3′-UTR shortening than TCGA breast cancer data, it changes the target sites of the common tamoMiRNAs. Since the NUDT21 KD experiment previously demonstrated the tumorigenic role of APA events in a miRNA dependent fashion, this result suggests that the APA-initiated tumorigenesis is attributable to the miRNA target site changes, not the APA events themselves. Further, we found that the miRNA target site changes identify tumor cell proliferation and immune cell infiltration to the tumor microenvironment better than the miRNA expression levels or the APA events themselves. Altogether, our computational analyses provide a proof-of-concept demonstration that the miRNA target site information indicates the effect of global APA events with a potential as predictive biomarker.

scholarly journals Alternative Polyadenylation Regulates Patient-specific Tumor Growth by Individualizing the MicroRNA Target Site Landscape

2019 ◽  
Author(s):  
Soyeon Kim ◽  
Yulong Bai ◽  
Zhenjiang Fan ◽  
Brenda Diergaarde ◽  
George C. Tseng ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Target Genes ◽  
Alternative Polyadenylation ◽  
Target Site ◽  
Patient Specific ◽  
Microrna Target ◽  
Cancer Etiology ◽  
Cancer Data ◽  
Specific Tumor ◽  
Target Sites

AbstractBackgroundAlternative polyadenylation (APA) shortens or lengthens the 3’-untranslated region (3’-UTR) of hundreds of genes in cancer. While APA genes modify microRNA target sites in the 3’-UTRs to promote tumorigenesis, previous studies have focused on a subset of the modification landscape.MethodFor comprehensive understanding of the function of global APA events, we consider the total target site landscape of microRNAs that are significantly and collectively modified by global APA genes. To identify such microRNAs in spite of complex interactions between microRNAs and the APA genes, we developedProbabilisticInference ofMicroRNATarget Site Modification throughAPA(PRIMATA-APA).ResultsRunning PRIMATA-APA on TCGA breast cancer data, we identified that global APA events concentrate to modify target sites of particular microRNAs (target-site-modified-miRNAor tamoMiRNA). TamoMiRNAs are enriched for microRNAs known to regulate cancer etiology and treatments. Also, their target genes are enriched in cancer-associated pathways, suggesting that APA modifies target sites of tamoMiRNAs to progress tumors. Knockdown of NUDT21, a master 3’-UTR regulator in HeLa cells, confirmed the causal role of tamoMiRNAs for tumor growth.ConclusionsFurther, the expressions of tamoMiRNA target genes, enriched in cancer-associated pathways, vary across tumor samples as a function of patient-specific APA events, suggesting that APA is a novel regulatory axis for interpatient tumor heterogeneity.

scholarly journals Position-wise binding preference is important for miRNA target site prediction

2020 ◽  
Vol 36 (12) ◽  
pp. 3680-3686
Author(s):  
Amlan Talukder ◽  
Xiaoman Li ◽  
Haiyan Hu
Keyword(s):  
Dynamic Programming ◽  
Markov Model ◽  
Mirna Target ◽  
Dynamic Programming Algorithm ◽  
Target Prediction ◽  
Target Site ◽  
Mirna Target Site ◽  
Supplementary Information ◽  
Target Sites ◽  
Target Binding

Abstract Motivation It is a fundamental task to identify microRNAs (miRNAs) targets and accurately locate their target sites. Genome-scale experiments for miRNA target site detection are still costly. The prediction accuracies of existing computational algorithms and tools are often not up to the expectation due to a large number of false positives. One major obstacle to achieve a higher accuracy is the lack of knowledge of the target binding features of miRNAs. The published high-throughput experimental data provide an opportunity to analyze position-wise preference of miRNAs in terms of target binding, which can be an important feature in miRNA target prediction algorithms. Results We developed a Markov model to characterize position-wise pairing patterns of miRNA–target interactions. We further integrated this model as a scoring method and developed a dynamic programming (DP) algorithm, MDPS (Markov model-scored Dynamic Programming algorithm for miRNA target site Selection) that can screen putative target sites of miRNA-target binding. The MDPS algorithm thus can take into account both the dependency of neighboring pairing positions and the global pairing information. Based on the trained Markov models from both miRNA-specific and general datasets, we discovered that the position-wise binding information specific to a given miRNA would benefit its target prediction. We also found that miRNAs maintain region-wise similarity in their target binding patterns. Combining MDPS with existing methods significantly improves their precision while only slightly reduces their recall. Therefore, position-wise pairing patterns have the promise to improve target prediction if incorporated into existing software tools. Availability and implementation The source code and tool to calculate MDPS score is available at http://hulab.ucf.edu/research/projects/MDPS/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals A variant affecting a putative miRNA target site in estrogen receptor (ESR) 1 is associated with breast cancer risk in premenopausal women

2008 ◽  
Vol 30 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Sandrine Tchatchou ◽  
Anke Jung ◽  
Kari Hemminki ◽  
Christian Sutter ◽  
Barbara Wappenschmidt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mirna Target ◽  
Premenopausal Women ◽  
Target Site ◽  
Mirna Target Site

Bayesian Frailty Model for Time to Event Breast Cancer Data

2011 ◽  
Vol 4 (2) ◽  
pp. 8-12
Author(s):  
Leo Alexander T Leo Alexander T ◽  
◽  
Pari Dayal L Pari Dayal L ◽  
Valarmathi S Valarmathi S ◽  
Ponnuraja C Ponnuraja C ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Frailty Model ◽  
Breast Cancer Data ◽  
Time To Event ◽  
Cancer Data

AGE FEATURES OF MOLECULAR-BIOLOGICAL SUBTYPES OF BREAST CANCER IN THE REPUBLIC OF UZBEKISTAN

2018 ◽  
Vol 64 (2) ◽  
pp. 196-199
Author(s):  
Gulya Miryusupova ◽  
G. Khakimov ◽  
N. Shayusupov
Keyword(s):  
Breast Cancer ◽  
Cancer Care ◽  
Indigenous Women ◽  
Morbidity And Mortality ◽  
Breast Cancer Data ◽  
Female Population ◽  
Cancer Data ◽  
Age Related ◽  
The Republic ◽  
Age Features

According to the results of breast cancer data in the Republic of Uzbekistan in addition to the increase in morbidity and mortality from breast cancer among women the presence of age specific features among indigenous women in the direction of “rejuvenating” of the disease with all molecular-biological (phenotypic) subtypes of breast cancer were marked. Within the framework of age-related features the prevalence of the least favorable phenotypes of breast cancer was found among indigenous women: Her2/neu hyperexpressive and three times negative subtype of breast cancer. The data obtained made it possible to build a so-called population “portrait” of breast cancer on the territory of the Republic, which in turn would contribute to further improvement of cancer care for the female population of the country.

Genetics testing firm is accused of "hiding vital breast cancer data"

BMJ ◽  
2012 ◽  
Vol 345 (nov01 2) ◽  
pp. e7402-e7402
Author(s):  
N. Hawkes
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Data ◽  
Cancer Data

Screening Breast MRI and Gadolinium Deposition: Cause for Concern?

2021 ◽  
Author(s):  
Colleen H Neal
Keyword(s):  
Breast Cancer ◽  
Renal Function ◽  
Contrast Agents ◽  
Biological Significance ◽  
Breast Mri ◽  
Reliable Data ◽  
Breast Cancer Data ◽  
Cancer Data ◽  
Contrast Enhanced ◽  
Gadolinium Retention

Abstract Gadolinium-based contrast agents (GBCAs) have been used worldwide for over 30 years and have enabled lifesaving diagnoses. Contrast-enhanced breast MRI is frequently used as supplemental screening for women with an elevated lifetime risk of breast cancer. Data have emerged that indicate a fractional amount of administered gadolinium is retained in the bone, skin, solid organs, and brain tissues of patients with normal renal function, although there are currently no reliable data regarding the clinical or biological significance of this retention. Linear GBCAs are associated with a higher risk of gadolinium retention than macrocyclic agents. Over the course of their lives, screened women may receive high cumulative doses of GBCA. Therefore, as breast MRI screening utilization increases, thoughtful use of GBCA is indicated in this patient population.

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