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Molecular Research of Nuclear Receptors and Oncology

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 7338

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Special Issue Editor

Prof. Dr. Kouichi Yoshinari

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Guest Editor

Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
Interests: nuclear receptors; Ah receptor; gene regulation; drug/xenobiotic metabolism; liver; hepatotoxicity; hepatocarcinogenesis

Special Issue Information

Dear Colleagues,

Nuclear receptors are a group of transcription factors that respond to endogenous and xenobiotic compounds. They play numerous physiological, pathophysiological, and toxicological functions in humans, including the synthesis, homeostasis, and actions of hormones and vitamins, energy metabolism and xenobiotic metabolism and disposition, by directly (through DNA binding) or indirectly (through protein–protein interaction) regulating gene expression. In the field of oncology, sex hormone-responsive nuclear receptors, such as estrogen receptor and androgen receptor, have been targets of cancer chemotherapy. In fact, a number of drugs targeting these receptors have been developed and used clinically. Not only agonists and antagonists but also selective modulators of these receptors’ functions are used, although their mechanisms of action are not fully understood. Xenobiotic-responsive nuclear receptors, such as CAR and PXR, are also drawing the attention of researchers from the viewpoint of chemical carcinogenesis and the metabolism and pharmacokinetics/pharmacodynamics of chemotherapeutic agents. Moreover, several nuclear receptors, including RORγ and NR4A1, have been reported to modulate immunity and inflammation. Due to a close relation between cancer and immunity/inflammation, nuclear receptors may become a novel target of cancer therapy. This Special Issue welcomes original and review manuscripts describing recent progress in nuclear receptor research in oncology at molecular levels.

Prof. Dr. Kouichi Yoshinari
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

gene regulation
protein–protein interaction
carcinogenesis
hormone-sensitive cancer
cancer chemotherapy
tumor marker
cancer stem cell

Published Papers (3 papers)

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Research

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17 pages, 6423 KiB

Open AccessArticle

The Novel RXR Agonist MSU-42011 Differentially Regulates Gene Expression in Mammary Tumors of MMTV-Neu Mice

by Lyndsey A. Reich, Ana S. Leal, Edmund Ellsworth and Karen T. Liby

Int. J. Mol. Sci. 2023, 24(5), 4298; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054298 - 21 Feb 2023

Cited by 1 | Viewed by 1645

Abstract

Retinoid X receptor (RXR) agonists, which activate the RXR nuclear receptor, are effective in multiple preclinical cancer models for both treatment and prevention. While RXR is the direct target of these compounds, the downstream changes in gene expression differ between compounds. RNA sequencing was used to elucidate the effects of the novel RXRα agonist MSU-42011 on the transcriptome in mammary tumors of HER2+ mouse mammary tumor virus (MMTV)-Neu mice. For comparison, mammary tumors treated with the FDA approved RXR agonist bexarotene were also analyzed. Each treatment differentially regulated cancer-relevant gene categories, including focal adhesion, extracellular matrix, and immune pathways. The most prominent genes altered by RXR agonists positively correlate with survival in breast cancer patients. While MSU-42011 and bexarotene act on many common pathways, these experiments highlight the differences in gene expression between these two RXR agonists. MSU-42011 targets immune regulatory and biosynthetic pathways, while bexarotene acts on several proteoglycan and matrix metalloproteinase pathways. Exploration of these differential effects on gene transcription may lead to an increased understanding of the complex biology behind RXR agonists and how the activities of this diverse class of compounds can be utilized to treat cancer. Full article

(This article belongs to the Special Issue Molecular Research of Nuclear Receptors and Oncology)

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14 pages, 1426 KiB

Open AccessArticle

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

by Yuichiro Kanno, Nao Saito, Naoya Yamashita, Kazuki Ota, Ryota Shizu, Takuomi Hosaka, Kiyomitsu Nemoto and Kouichi Yoshinari

Int. J. Mol. Sci. 2022, 23(20), 12095; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012095 - 11 Oct 2022

Cited by 1 | Viewed by 1374

Abstract

Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ΔNp63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ΔNp63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ΔNp63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers. Full article

(This article belongs to the Special Issue Molecular Research of Nuclear Receptors and Oncology)

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Review

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22 pages, 1117 KiB

Open AccessReview

The Role of Androgen Receptor and microRNA Interactions in Androgen-Dependent Diseases

by Agnieszka Bielska, Anna Skwarska, Adam Kretowski and Magdalena Niemira

Int. J. Mol. Sci. 2022, 23(3), 1553; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031553 - 28 Jan 2022

Cited by 5 | Viewed by 3557

Abstract

The androgen receptor (AR) is a member of the steroid hormone receptor family of nuclear transcription factors. It is present in the primary/secondary sexual organs, kidneys, skeletal muscles, adrenal glands, skin, nervous system, and breast. Abnormal AR functioning has been identified in numerous diseases, specifically in prostate cancer (PCa). Interestingly, recent studies have indicated a relationship between the AR and microRNA (miRNA) crosstalk and cancer progression. MiRNAs are small, endogenous, non-coding molecules that are involved in crucial cellular processes, such as proliferation, apoptosis, or differentiation. On the one hand, AR may be responsible for the downregulation or upregulation of specific miRNA, while on the other hand, AR is often a target of miRNAs due to their regulatory function on AR gene expression. A deeper understanding of the AR–miRNA interactions may contribute to the development of better diagnostic tools as well as to providing new therapeutic approaches. While most studies usually focus on the role of miRNAs and AR in PCa, in this review, we go beyond PCa and provide insight into the most recent discoveries about the interplay between AR and miRNAs, as well as about other AR-associated and AR-independent diseases. Full article

(This article belongs to the Special Issue Molecular Research of Nuclear Receptors and Oncology)

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