ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature

Roy, Lynn; Samyesudhas, Serene; Carrasco, Martín; Li, Jun; Joseph, Stancy; Dahl, Richard; Dahl, Karen D. Cowden

doi:10.18632/oncotarget.2247

Cited by 23 publications

(35 citation statements)

References 31 publications

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“…Results are shown in Supplemental Table 3, Figure 3E. FUBP1, which regulates c-Myc gene transcription, had significantly higher inferred activity in BASAL-BRCA compared to gynecologic tumors; ARID3B activity was significantly higher in OV, consistent with its role in promoting ovarian tumor development, in part by regulating stem cell genes [18]; NR5A2 (also known as liver receptor homolog-1, LRH-1) was significantly higher in uterine endometriod tumors, consistent with its function in regulating metabolism and hormone synthesis. Also in agreement with previous reports, WT1 activity was significantly higher in ovarian serous [19] and uterine sarcoma [20]; TWIST1, a central player in the EMT, had increased activity in ovarian serous [21] and uterine serous cancers; YY1, which regulates various processes of development and differentiation and is involved in tumorigenesis of breast and ovarian cancer [22], had increased activity in these cancers.…”

Section: Multitask Regression Identifies Tumor Type-specific Tfs Assomentioning

confidence: 76%

Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers

Osmanbeyoglu

Shimizu

Rynne-Vidal

et al. 2018

Preprint

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Epigenomic data on transcription factor occupancy and chromatin accessibility can elucidate the developmental origin of cancer cells and reveal the enhancer landscape of key oncogenic transcriptional regulators. However, in many cancers, epigenomic analyses have been limited, and computational methods to infer regulatory networks in tumors typically use expression data alone, or rely on transcription factor (TF) motifs in annotated promoter regions. Here, we develop a novel machine learning strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to combine cell line chromatin accessibility data with large tumor expression data sets and model the effect of enhancers on transcriptional programs in multiple cancers. We generated a new ATAC-seq data set profiling chromatin accessibility in gynecologic and basal breast cancer cell lines and applied PSIONIC to 723 RNA-seq experiments from ovarian, uterine, and basal breast tumors as All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/333757 doi: bioRxiv preprint first posted online May. 30, 2018; 2 well as 96 cell line RNA-seq profiles. Our computational framework enables us to share information across tumors to learn patient-specific inferred TF activities, revealing regulatory differences between and within tumor types. Many of the identified TF regulators were significantly associated with survival outcome in basal breast, uterine serous and endometrioid carcinomas. Moreover, PSIONIC-predicted activity for MTF1 in cell line models correlated with sensitivity to MTF1 inhibition. Therefore computationally dissecting the role of TFs in gynecologic cancers may ultimately advance personalized therapy.

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Section: Multitask Regression Identifies Tumor Type-specific Tfs Assomentioning

confidence: 76%

Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers

Osmanbeyoglu

Shimizu

Rynne-Vidal

et al. 2018

Preprint

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“…ARID3B and its paralog ARID3A are expressed in ESCs in a complex with NANOG, OCT4, and NAC1 84 . ARID3B is overexpressed in serous ovarian cancer and its expression in the nucleus correlates with relapse following chemotherapy 58,91 . ARID3B increases expression of stem cell markers 92 .…”

Section: Transcription Factorsmentioning

confidence: 99%

Can Stemness and Chemoresistance be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

Roy

Dahl²

2018

Preprint

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Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.

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“…ARID3B binds with ARID3A and KDM4C to form the ARID3B-complex. The ARID3B-complex plays a vital role in cell proliferation by transcriptional regulation of stemness genes including HMGA1, c-MYC, vascular endothelial growth factor A (VEGF-A), and Wnt family member 1 (WNT1) [18,34,[55][56][57][58][59]. ARID3B knockout in immortalized first trimester human trophoblast cells results in reduced proliferation of these cells [18].…”

Section: Introductionmentioning

confidence: 99%

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

Ali

Stenglein

Spencer

et al. 2020

IJMS

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LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy.

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ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature

Cited by 23 publications

References 31 publications

Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers

Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers

Can Stemness and Chemoresistance be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

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