Vitamin D receptor-binding site variants affect prostate cancer progression

Lin, Victor C.; Huang, Shu Pin; Ting, Huei-Ju; Lung, Wen; Yu, Chia Cheng; Huang, Chao Yuan; Yin, Hsin Ling; Huang, Tsung Yi; Lee, Cheng Hsueh; Chang, Ta Yuan; Lu, Te‐Ling; Bao, Bo

doi:10.18632/oncotarget.18271

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…Numerous epidemiological studies have shown the association between the amount of dietary vitamin D, vitamin D level in circulation, and sunlight exposure with prostate cancer risk [71]. In addition, genetic polymorphisms in VDR were associated with prostate cancer susceptibility and prostate cancer progression [72,73,74]. VDR-knockout mice showed higher cell proliferation than wild-type mice [75].…”

Section: Subfamilies Of Nrsmentioning

confidence: 99%

The Role of Nuclear Receptors in Prostate Cancer

Shiota

Fujimoto

Kashiwagi

et al. 2019

Cells

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The nuclear receptor (NR) superfamily consists of 48 members that are divided into seven subfamilies. NRs are transcription factors that play an important role in a number of biological processes. The NR superfamily includes androgen receptor, which is a key player in prostate cancer pathogenesis, suggesting the functional roles of other NRs in prostate cancer. The findings on the roles of NRs in prostate cancer thus far have shown that several NRs such as vitamin D receptor, estrogen receptor β, and mineralocorticoid receptor play antioncogenic roles, while other NRs such as peroxisome proliferator-activated receptor γ and estrogen receptor α as well as androgen receptor play oncogenic roles. However, the roles of other NRs in prostate cancer remain controversial or uninvestigated. Further research on the role of NRs in prostate cancer is required and may lead to the development of novel preventions and therapeutics for prostate cancer.

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Section: Subfamilies Of Nrsmentioning

confidence: 99%

The Role of Nuclear Receptors in Prostate Cancer

Shiota

Fujimoto

Kashiwagi

et al. 2019

Cells

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“…Low expression of TUSC-3 was shown to correspond with poor PCa prognosis in patients, and TUSC-3 silencing enhanced cell migration and growth. 62 However, 1,25-Vitamin D strongly induced the expression of TUSC-3 in PCa cells. In a Phase II clinical trial, PCa patients with the highest serum levels of prostatic 1,25(OH)2D also had low COX-2 levels, but exhibited high IL-6 levels in their stroma tissue.…”

Section: Introductionmentioning

confidence: 97%

“… 51 , 53 , 62 , 63 In Taiwanese PCa patients, genetic variants, HFE rs9393682, and TUSC-3 rs1378033 were associated with time to progression in localized disease and low risk of advanced PCa for patients undergoing androgen deprivation therapy. 62 Furthermore, in vitro studies revealed 1,25-Vitamin D downregulated HFE and when silenced HFE impedes cell proliferation and wound healing. Low expression of TUSC-3 was shown to correspond with poor PCa prognosis in patients, and TUSC-3 silencing enhanced cell migration and growth.…”

Section: Introductionmentioning

confidence: 99%

“…103 VDR-related variants, HFE (rs9393682) and TUSC3 (rs1378033) , were linked to disease progression in patients with localized tumors (post surgery) and advanced PCA (post androgen deprivation) in two independent cohorts, respectively. 62 Although both circulating vitamin E plasma levels and intervention have been shown to modulate PCa risk, Vitamin E genetic polymorphisms also influence patient predisposition to develop this malignancy. During vitamin E intervention, inheritance of variants in vitamin E-related genes, SEC14L2 , SOD1 , and TTPA , significantly modified risk of high-grade PCa in patients.…”

Section: Introductionmentioning

confidence: 99%

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Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations

2018

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Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer mortality in American males. Notably, men of African descent in the United States and Caribbean have the highest PCa mortality rates compared to men with European ancestry. Although current therapeutics are quite potent and effective, disease resistance, progression to metastasis, therapy-associated toxicities and efficacy-related issues in diverse populations develop over time. Thus, non-toxic and efficacious therapeutic strategies are needed to address these major obstacles for the clinical treatment and management of PCa. In this regard, preclinical and population-based efficacy studies have shown the potential of natural non-toxic nutraceuticals as potent anti-PCa agents. Accordingly, the implementation of nutraceutical intervention and genetic testing in diverse populations might aid in the development and design of precision medicine strategies to reduce the burden of chemotherapy-associated toxicities, suppress disease resistance, and treat both localized and advanced PCa. Consequently, additional large-scale and inclusive clinical studies are required to fully assess efficacy and therapeutic limitations of these agents in PCa. This review discusses the most current clinical research on selected nutraceutical agents and their efficacy in the context of clinico-pathological outcomes and disease susceptibility in diverse PCa clinical and epidemiological studies.

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“…As a non-coding single-stranded RNA, miRNA affects the biological functions of cells through its complete or incomplete complementary binding to the 3'-end of target genes (4,5). miR-129 is a miRNA located in the genomic region near the fragile site of chromosome 7q (6), and fragile site loss is closely related to the malignancy of prostate cancer (7). miR-129-3p is a miRNA closely correlated with the development and progression of tumors and the expression is low in gastric cancer (8) and breast cancer (9), functioning as a tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

Effects of miR‑129‑3p on biological functions of prostate cancer cells through targeted regulation of Smad3

2019

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Effects of miR-129-3p on the biological functions of prostate cancer cells through the targeted regulation of Smad3 were investigated. RT-PCR was used to detect the expression levels of miR-129-3p in prostate cancer tissues and cells and its target gene Smad3 mRNA determined by bioinformatics prediction. Correlation between miR-129-3p and Smad3 was analyzed. MTT assay, cell invasion detection, and apoptosis detection were conducted to detect the effects of miR-129-3p and Smad3 on the proliferation, invasion, and apoptosis of prostate cancer cells. The results of RT-qPCR showed that the expression level of miR-129-3p decreased but that of Smad3 increased in the prostate cancer tissue, and the expression levels of the two were significantly and negatively correlated. Additionally, the expression levels were closely related to the degree of tumor differentiation, TNM staging, and lymph node metastasis (P<0.05). Bioinformatics prediction and subsequent experiments proved that Smad3 was the direct target gene of miR-129-3p. Cell detection confirmed that the overexpression of miR-129-3p or the inhibition of Smad3 expression inhibited the proliferation and invasion of prostate cancer cells, promoting apoptosis, and increased the expression level of pro-apoptotic protein Bax, as well as decreased the expression level of anti-apoptotic protein Bcl-2. Inhibition of miR-129-3p expression had the opposite effect to overexpression. miR-129-3p, which may be a new and potential target for the treatment of prostate cancer, can inhibit the proliferation and invasion of prostate cancer cells and promote their apoptosis by directly targeting Smad3.

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Vitamin D receptor-binding site variants affect prostate cancer progression

Cited by 10 publications

References 26 publications

The Role of Nuclear Receptors in Prostate Cancer

The Role of Nuclear Receptors in Prostate Cancer

Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations

Effects of miR‑129‑3p on biological functions of prostate cancer cells through targeted regulation of Smad3

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