NAD(P)H-quinone oxidoreductase 1 silencing aggravates hormone-induced prostatic hyperplasia in mice

Kim, H.-T.; Kim, Y.-J.; Park, S.-R.; Ryu, Si-Yun; Jung, Jongwan

doi:10.1111/and.12906

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…This family of isomerases contains a tetratricopeptide repeat domain that allows them to interact and regulate HSP90 (Heat Shock Protein 90) 56 . Animal studies suggest that HSP90 can promote prostate hyperplasia by activating the classical complement pathway or by enhancing testosterone‐induced nuclear AR expression 57,58 . Whether these alterations are drivers or passengers in BPH progression requires more investigation; however, their increased frequency does justify that investigation.…”

Section: Discussionmentioning

confidence: 99%

Whole‐exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways

White,

Kaninjing,

Adeniji

et al. 2024

The Prostate

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BackgroundThrough whole‐exome sequencing of 60 formalin‐fixed paraffin‐embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non‐European populations are lacking.MethodsIn this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH.ResultsTwo hundred and two nonbenign, ClinVar‐annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co‐occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co‐occurring interactions. Two hundred and seventy‐nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11‐595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair.ConclusionsNGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

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Section: Discussionmentioning

confidence: 99%

Whole‐exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways

White,

Kaninjing,

Adeniji

et al. 2024

The Prostate

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“…111 Kim et al reported that a deficiency of the nitroquinoline 1-oxide (NQO1) enzyme, which is an flavin adenine dinucleotide dependent flavoprotein that performs various functions in the cellular defense system, increased the expression of HSP90, which increases the affinity of AR for testosterone and can be responsible for enlargement of the prostate gland in NQO1 knockout mice. 112…”

Section: Heat Shock Proteinsmentioning

confidence: 99%

Intrinsic and extrinsic factors causing hyperplasia of the prostate

Kyoda,

Shibamori,

Shindo

et al. 2024

Int J of Urology

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Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.

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“…Another study on the role of HSP90 in the development of BPH was carried out on a murine model with induced prostate hyperplasia and on human cell lines (LNCaP, BPH-1, WPMY-1), where the role of NAD(P)H-quinone oxidoreductase 1 (NQO1) was analyzed, a FAD-dependent flavoprotein, involved in the defense processes in the cell and preventing the degradation of the p53 protein, in the exacerbation of prostate tissue cell hyperplasia [114]. This study showed that the deficiency of the NQO1 enzyme increases the expression of HSP90, which increases the affinity of AR for testosterone and can be responsible for the enlargement of the prostate gland in NQO1-/-mice.…”

Section: Hsp90 and Prostate Cancer And Benign Prostatic Hyperplasiamentioning

confidence: 99%

Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer

Ratajczak

Lubkowski

Lubkowska

2022

IJMS

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Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)—a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.

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NAD(P)H-quinone oxidoreductase 1 silencing aggravates hormone-induced prostatic hyperplasia in mice

Cited by 6 publications

References 28 publications

Whole‐exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways

Whole‐exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways

Intrinsic and extrinsic factors causing hyperplasia of the prostate

Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer

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