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Article ; Online: MicroRNA-4287 is a novel tumor suppressor microRNA controlling epithelial-to mesenchymal transition in prostate cancer.

Bhagirath, Divya / Yang, Thao Ly / Akoto, Theresa / Patel, Nikhil / Tabatabai, Laura Z / Saini, Sharanjot

2020 Volume 11, Issue 51, Page(s) 4681–4692

Abstract: Prostate cancer (PCa) is a significant cause of male morbidity in the United States. Despite recent advances in diagnosis and therapeutic interventions, significant fraction of cases still progress to an advanced stage. Various genetic/epigenetic ... ...

Abstract	Prostate cancer (PCa) is a significant cause of male morbidity in the United States. Despite recent advances in diagnosis and therapeutic interventions, significant fraction of cases still progress to an advanced stage. Various genetic/epigenetic elements that facilitate this progression are not yet completely known and the mechanism that favors advanced disease is an area of investigation. A characteristic feature associated with progressive disease is deletion of chromosome 8p (chr8p) region, that harbors tumor-suppressor
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27849
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Article ; Online: Polyethylene Glycol 20k. Does It Fluoresce?

Laatsch, Bethany F / Brandt, Michael / Finke, Brianna / Fossum, Carl J / Wackett, Miles J / Lowater, Harrison R / Narkiewicz-Jodko, Alex / Le, Christine N / Yang, Thao / Glogowski, Elizabeth M / Bailey-Hartsel, Scott C / Bhattacharyya, Sudeep / Hati, Sanchita

ACS omega

2023 Volume 8, Issue 15, Page(s) 14208–14218

Abstract: Polyethylene glycol (PEG) is a polyether compound commonly used in biological research and medicine because it is biologically inert. This simple polymer exists in variable chain lengths (and molecular weights). As they are devoid of any contiguous π- ... ...

Abstract	Polyethylene glycol (PEG) is a polyether compound commonly used in biological research and medicine because it is biologically inert. This simple polymer exists in variable chain lengths (and molecular weights). As they are devoid of any contiguous π-system, PEGs are expected to lack fluorescence properties. However, recent studies suggested the occurrence of fluorescence properties in non-traditional fluorophores like PEGs. Herein, a thorough investigation has been conducted to explore if PEG 20k fluoresces. Results of this combined experimental and computational study suggested that although PEG 20k could exhibit "through-space" delocalization of lone pairs of electrons in aggregates/clusters, formed via intermolecular and intramolecular interactions, the actual contributor of fluorescence between 300 and 400 nm is the stabilizer molecule, i.e., 3-
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c01124
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Article: MicroRNAs as Regulators of Prostate Cancer Metastasis.

Bhagirath, Divya / Yang, Thao Ly / Dahiya, Rajvir / Saini, Sharanjot

Advances in experimental medicine and biology

2018 Volume 1095, Page(s) 83–100

Abstract: Prostate cancer causes significant morbidity in men and metastatic disease is a major cause of cancer related deaths. Prostate metastasis is controlled by various cellular intrinsic and extrinsic factors, which are often under the regulatory control of ... ...

Abstract	Prostate cancer causes significant morbidity in men and metastatic disease is a major cause of cancer related deaths. Prostate metastasis is controlled by various cellular intrinsic and extrinsic factors, which are often under the regulatory control of various metastasis-associated genes. Given the dynamic nature of metastatic cancer cells, the various factors controlling this process are themselves regulated by microRNAs which are small non-coding RNAs. Significant research work has shown differential microRNA expression in primary and metastatic prostate cancer suggesting their importance in prostate pathogenesis. We will review the roles of different microRNAs in controlling the various steps in prostate metastasis.
MeSH term(s)	Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics ; Neoplasm Metastasis/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2018-07-23
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-95693-0_5
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Article: Significance of Proline Residue on Short Mucin Peptide Interactions with Mouse MUC1 Monoclonal Antibody Studied by Saturation Transfer Difference NMR Spectroscopy.

Her, Cheng / Westler, William M / Yang, Thao

JSM Chemistry

2013 Volume 1, Issue 1

Abstract: In this study we investigated to see whether or not a shortened MUC1 mucin peptide epitope with the sequence GVTSAPD containing a single prolyl residue would still bind specific monoclonal antibody as its native sequence (e.g., PDTRP), known to be the ... ...

Abstract	In this study we investigated to see whether or not a shortened MUC1 mucin peptide epitope with the sequence GVTSAPD containing a single prolyl residue would still bind specific monoclonal antibody as its native sequence (e.g., PDTRP), known to be the specific recognition site on the Variable Number Tandem Repeat (VNTR) region of MUC1 mucin by the immune system. The affinity of GVTSAPD peptide to a mouse Muc1 mucin specific monoclonal antibody (clone 6A4, IgG1 isotype) was investigated by Saturation Transfer Difference NMR spectroscopy (STD NMR). Results showed that the shortened mucin epitope GVTSAPD still retained affinity to Muc1 specific monoclonal antibody (mAb) while one that lacks the prolyl residue at position 6 lost its affinity, which suggests that P
Language	English
Publishing date	2013-10-17
Publishing country	United States
Document type	Journal Article
ISSN	2334-1831
ISSN	2334-1831
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Article: BRN4

Bhagirath, Divya / Yang, Thao Ly / Tabatabai, Z Laura / Majid, Shahana / Dahiya, Rajvir / Tanaka, Yuichiro / Saini, Sharanjot

Clinical cancer research : an official journal of the American Association for Cancer Research

2019 Volume 25, Issue 21, Page(s) 6532–6545

Abstract: Purpose: Neuroendocrine prostate cancer (NEPC), an aggressive variant of castration-resistant prostate cancer (CRPC), often emerges after androgen receptor-targeted therapies such as enzalutamide or : Results: We identify for the first time that: (i) ...

Abstract	Purpose: Neuroendocrine prostate cancer (NEPC), an aggressive variant of castration-resistant prostate cancer (CRPC), often emerges after androgen receptor-targeted therapies such as enzalutamide or Results: We identify for the first time that: (i) Conclusions: Our study identifies a novel TF that drives NEPC and suggests that as adaptive mechanism to enzalutamide treatment, prostate cancer cells express and secrete
MeSH term(s)	Aged ; Aged, 80 and over ; Animals ; Carcinogenesis/genetics ; Carcinoma, Neuroendocrine/genetics ; Carcinoma, Neuroendocrine/pathology ; Cell Differentiation/genetics ; Cell Line, Tumor ; Disease Progression ; Extracellular Vesicles/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Heterografts ; Homeodomain Proteins/genetics ; Humans ; Male ; Mice ; Middle Aged ; POU Domain Factors/genetics ; Prostate/metabolism ; Prostate/pathology ; Prostatic Neoplasms, Castration-Resistant/epidemiology ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology ; Receptors, Androgen/genetics
Chemical Substances	AR protein, human ; Homeodomain Proteins ; POU Domain Factors ; POU3F4 protein, human ; Receptors, Androgen ; transcription factor Brn-2
Language	English
Publishing date	2019-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-0498
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Zs.A 4223: Show issues

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Article ; Online: Role of a novel race-related tumor suppressor microRNA located in frequently deleted chromosomal locus 8p21 in prostate cancer progression.

Bhagirath, Divya / Yang, Thao Ly / Tabatabai, Z Laura / Shahryari, Varahram / Majid, Shahana / Dahiya, Rajvir / Tanaka, Yuichiro / Saini, Sharanjot

Carcinogenesis

2019 Volume 40, Issue 5, Page(s) 633–642

Abstract: The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21-22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this ... ...

Abstract	The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21-22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes-miR-3622, miR-3622b, miR-383-that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p-miR-4288-by employing clinical samples and cell lines. Our data suggests that (i) miR-4288 is widely downregulated in primary prostate tumors and cell lines; (ii) miR-4288 expression is lost in metastatic castration-resistant PCa; (ii) miR-4288 downregulation is race-related PCa alteration that is prevalent in Caucasian patients and not in African Americans; (iii) in Caucasians, miR-4288 was found to be associated with increasing tumor grade and high serum prostate-specific antigen, suggesting that miR-4288 downregulation/loss may be associated with tumor progression specifically in Caucasians; (iv) miR-4288 possess significant potential as a molecular biomarker to predict aggressiveness/metastasis; and (v) miR-4288 is anti-proliferative, is anti-invasive and inhibits epithelial-to-mesenchymal transition; and (vi) miR-4288 directly represses expression of metastasis/invasion-associated genes MMP16 and ROCK1. Thus, the present study demonstrates a tumor suppressor role for a novel miRNA located with a frequently lost region in PCa, strengthening our hypothesis that this locus is causally related to PCa disease progression via loss of microRNA genes. Our study suggests that miR-4288 may be a novel biomarker and therapeutic target, particularly in Caucasians.
MeSH term(s)	Adult ; Aged ; Apoptosis ; Cell Movement ; Cell Proliferation ; Chromosome Deletion ; Chromosomes, Human, Pair 8/genetics ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Male ; MicroRNAs/genetics ; Middle Aged ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Tumor Cells, Cultured
Chemical Substances	MIRN4288 microRNA, human ; MicroRNAs
Language	English
Publishing date	2019-03-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgz058
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Zs.A 1558: Show issues

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Article ; Online: microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer.

Bhagirath, Divya / Yang, Thao Ly / Bucay, Nathan / Sekhon, Kirandeep / Majid, Shahana / Shahryari, Varahram / Dahiya, Rajvir / Tanaka, Yuichiro / Saini, Sharanjot

Cancer research

2018 Volume 78, Issue 7, Page(s) 1833–1844

Abstract: Because of high heterogeneity, molecular characterization of prostate cancer based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be ... ...

Abstract	Because of high heterogeneity, molecular characterization of prostate cancer based on biopsy sampling is often challenging. Hence, a minimally invasive method to determine the molecular imprints of a patient's tumor for risk stratification would be advantageous. In this study, we employ a novel, digital amplification-free quantification method using the nCounter technology (NanoString Technologies) to profile exosomal serum miRNAs (ex-miRNA) from aggressive prostate cancer cases, benign prostatic hyperplasia, and disease-free controls. We identified several dysregulated miRNAs, one of which was the tumor suppressor miR-1246. miR-1246 was downregulated in prostate cancer clinical tissues and cell lines and was selectively released into exosomes. Overexpression of miR-1246 in a prostate cancer cell line significantly inhibited xenograft tumor growth
MeSH term(s)	Animals ; Apoptosis/genetics ; Biomarkers, Tumor/genetics ; Cadherins/metabolism ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cell Survival/genetics ; Epithelial-Mesenchymal Transition/genetics ; Exosomes/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Mice, Nude ; MicroRNAs/genetics ; Neoplasm Transplantation ; PC-3 Cells ; Prostate/pathology ; Prostatic Hyperplasia/genetics ; Prostatic Hyperplasia/pathology ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Transplantation, Heterologous ; Vimentin/metabolism
Chemical Substances	Biomarkers, Tumor ; Cadherins ; MIRN1246 microRNA, human ; MicroRNAs ; Vimentin
Language	English
Publishing date	2018-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-17-2069
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Uh III Zs.135/5: Show issues

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Article ; Online: MicroRNA determinants of neuroendocrine differentiation in metastatic castration-resistant prostate cancer.

Bhagirath, Divya / Liston, Michael / Patel, Nikhil / Akoto, Theresa / Lui, Byron / Yang, Thao Ly / To, Dat My / Majid, Shahana / Dahiya, Rajvir / Tabatabai, Z Laura / Saini, Sharanjot

Oncogene

2020 Volume 39, Issue 49, Page(s) 7209–7223

Abstract: Therapy-induced neuroendocrine prostate cancer (NEPC), an extremely aggressive variant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread use of highly potent androgen receptor (AR)-pathway inhibitors (APIs) ... ...

Abstract	Therapy-induced neuroendocrine prostate cancer (NEPC), an extremely aggressive variant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread use of highly potent androgen receptor (AR)-pathway inhibitors (APIs) such as Enzalutamide (ENZ) and Abiraterone and arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED). The molecular basis of NED is not completely understood leading to a lack of effective molecular markers for its diagnosis. Here, we demonstrate for the first time, that lineage switching to NE states is accompanied by key miRNA alterations including downregulation of miR-106a~363 cluster and upregulation of miR-301a and miR-375. To systematically investigate the key miRNAs alterations driving therapy-induced NED, we performed small RNA-NGS in a retrospective cohort of human metastatic CRPC clinical samples + PDX models with adenocarcinoma features (CRPC-adeno) vs those with neuroendocrine features (CRPC-NE). Further, with the application of machine learning algorithms to sequencing data, we trained a 'miRNA classifier' that could robustly classify 'CRPC-NE' from 'CRPC-Adeno' cases. The performance of classifier was validated in an additional cohort of mCRPC patients and publicly available PCa cohorts. Importantly, we demonstrate that miR-106a~363 cluster pleiotropically regulate cardinal nodal proteins instrumental in driving NEPC including Aurora Kinase A, N-Myc, E2F1 and STAT3. Our study has important clinical implications and transformative potential as our 'miRNA classifier' can be used as a molecular tool to stratify mCRPC patients into those with/without NED and guide treatment decisions. Further, we identify novel miRNA NED drivers that can be exploited for NEPC therapeutic targeting.
MeSH term(s)	Aurora Kinase A/metabolism ; Cell Line, Tumor ; Humans ; Male ; MicroRNAs/genetics ; Neoplasm Metastasis ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology
Chemical Substances	MicroRNAs ; Aurora Kinase A (EC 2.7.11.1)
Language	English
Publishing date	2020-10-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-01493-8
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Zs.A 2218: Show issues

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Article ; Online: A novel microRNA regulator of prostate cancer epithelial-mesenchymal transition.

Bucay, Nathan / Bhagirath, Divya / Sekhon, Kirandeep / Yang, Thao / Fukuhara, Shinichiro / Majid, Shahana / Shahryari, Varahram / Tabatabai, ZLaura / Greene, Kirsten L / Hashimoto, Yutaka / Shiina, Marisa / Yamamura, Soichiro / Tanaka, Yuichiro / Deng, Guoren / Dahiya, Rajvir / Saini, Sharanjot

Cell death and differentiation

2017 Volume 24, Issue 7, Page(s) 1263–1274

Abstract: The most frequent alteration in the prostate oncogenome is loss of chromosome (chr) 8p21 that has been associated with loss of NKX3.1 homeobox gene. Chr8p21 deletions increase significantly with tumor grade and are associated with poor prognosis in ... ...

Abstract	The most frequent alteration in the prostate oncogenome is loss of chromosome (chr) 8p21 that has been associated with loss of NKX3.1 homeobox gene. Chr8p21 deletions increase significantly with tumor grade and are associated with poor prognosis in prostate cancer (PCa), suggesting critical involvement of this region in tumor progression. Recent studies suggest that apart from NKX3.1, this region harbors alternative tumor suppressors that are yet undefined. We proposed a novel, paradigm shifting hypothesis that this locus is associated with a miRNA gene cluster-miR-3622a/b- that plays a crucial suppressive role in PCa. Here we demonstrate the crucial role of miR-3622a in prostate cancer epithelial-to-mesenchymal transition (EMT). MicroRNA expression profiling in microdissected human PCa clinical tissues showed that miR-3622a expression is widely downregulated and is significantly correlated with poor survival outcome and tumor progression. To understand the functional significance of miR-3622a, knockdown and overexpression was performed using non-transformed prostate epithelial and PCa cell lines, respectively, followed by functional assays. Our data demonstrate that endogenous miR-3622a expression is vital to maintain the epithelial state of normal and untransformed prostate cells. miR-3622a expression inhibits EMT, progression and metastasis of PCa in vitro and in vivo. Further, we found that miR-3622a directly targets EMT effectors ZEB1 and SNAI2. In view of these data, we propose that frequent loss of miR-3622a at chr8p21 region leads to induction of EMT states that in turn, promotes PCa progression and metastasis. This study has potentially significant implications in the field of prostate cancer as it identifies an important miRNA component of a frequently lost chromosomal region with critical roles in prostate carcinogenesis which is a highly significant step towards understanding the mechanistic involvement of this locus. Also, our study indicates that miR-3622a is a novel PCa biomarker and potential drug target for developing therapeutic regimens against advanced PCa.
MeSH term(s)	Animals ; Base Sequence ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Chromosomes, Human, Pair 8/genetics ; DNA Methylation/genetics ; Disease Progression ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genome, Human ; Homeodomain Proteins/metabolism ; Humans ; Male ; Mice, Nude ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Prognosis ; Promoter Regions, Genetic/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Transcription Factors/metabolism
Chemical Substances	Homeodomain Proteins ; MicroRNAs ; NKX3-1 protein, human ; Neoplasm Proteins ; Transcription Factors
Language	English
Publishing date	2017-05-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/cdd.2017.69
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Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 80: Show issues

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