1.MicroRNAs and prostate cancer.
Wen-ting XU ; Ying-jie JIA ; Xiao-jiang LI ; Jun CHEN
National Journal of Andrology 2015;21(5):458-462
Prostate cancer (PCa) is one of the most common malignancies in the urinary system of males. A growing number of studies have shown that microRNAs, as small ribonucleic acid molecules and a class of non-coding small RNAs, are closely related with PCa and a variety of microRNAs are abnormally expressed in it. This article focuses on the roles of microRNAs in the occurrence and progression of PCa, with a description of differentially expressed microRNAs in PCa and an analysis of their association with its prognosis as well as their correlation with chemotherapy, androgen receptors, and metastasis of PCa.
Disease Progression
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Humans
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Male
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MicroRNAs
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metabolism
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Prognosis
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Prostatic Neoplasms
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chemistry
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genetics
;
metabolism
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Receptors, Androgen
;
metabolism
2.Up-regulation of androgen receptor by heat shock protein 27 and miR-1 induces pathogenesis of androgenic alopecia.
Journal of Central South University(Medical Sciences) 2022;47(1):72-78
OBJECTIVES:
The pathogenesis of androgenetic alopecia (AGA) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms.
METHODS:
A total of 46 male AGA patients (AGA group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected.
RESULTS:
The levels of DHT and HSP27 in the AGA group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of AGA group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05).
CONCLUSIONS
HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.
Alopecia/pathology*
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HSP27 Heat-Shock Proteins/metabolism*
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Humans
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Male
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MicroRNAs/genetics*
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RNA, Messenger
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Receptors, Androgen/metabolism*
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Up-Regulation
3.Molecular mechanisms of leupaxin involved in prostate carcinoma metastasis.
Guo-Hua ZHU ; Hai-Ping DAI ; Qun SHEN
National Journal of Andrology 2013;19(6):555-558
Leupaxin (LPXN) is a new member of the Paxillin superfamily, mainly located in focal adhesion plaques, involved in the transduction of multiple signaling pathways, and regulating the proliferation, adhesion and migration of tumor cells. In prostate cancer cells, LPXN is not only involved in the integrin signaling transduction pathway, regulating the proliferation, adhesion and migration of prostate cancer cells, but is also a new androgen receptor (AR) coactivator, regulating the transcription of nuclear AR effect genes, participating in AR signal transduction, and regulating the differentiation and invasion of prostate cancer cells. This review focuses on the molecular structure, special roles and molecular mechanisms of LPXN involved in prostatic carcinoma metastasis.
Cell Adhesion Molecules
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genetics
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metabolism
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Humans
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Male
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Neoplasm Metastasis
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Phosphoproteins
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genetics
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metabolism
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Prostatic Neoplasms
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genetics
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metabolism
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pathology
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Receptors, Androgen
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metabolism
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Signal Transduction
4.Expression characteristics of the USP24 gene in the mouse testis during spermatogenesis.
Qi-Yi HU ; Qiong DENG ; Jian-Wen ZHANG ; Fan ZHI ; Rui SUN ; Hui LIANG
National Journal of Andrology 2017;23(11):963-968
Objective:
To investigate the expression characteristics of the USP24 gene in the mouse testis and its role in spermatogenesis.
METHODS:
We examined the expression characteristics of USP24 in the testis tissues of wild-type mice at different postnatal weeks (PNW) and androgen receptor (AR)-knockout (ARKO) adult mice using real-time quantitative PCR and immunofluorescence, and detected the transcriptional activity of the USP24 promoter by dual-luciferase reporter gene assay.
RESULTS:
The expression of the USP24 gene was low in the testis tissue of the wild-type mice at PNW 1, increased dramatically at PNW 3 and stayed at a similar level till PNW 8. The USP24 protein was located mainly in the cytoplasm of Sertoli and spermatogenic cells. Compared with the wild-type, the adult ARKO mice showed a decreased expression of USP24 localized in the posterior head and mid-piece of the mature sperm in the testis. Dual-luciferase reporter gene assay showed that the transcriptional activity of the USP24 promoter was increased after testosterone stimulation.
CONCLUSIONS
The increased expression of the USP24 gene was associated with the initiation of sexual development, and the USP24 protein was expressed in the mature sperm of the mice. USP24 is an AR-target gene, which may be involved in the regulation of spermatogenesis in mice.
Animals
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Male
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Mice
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Mice, Knockout
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Promoter Regions, Genetic
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Receptors, Androgen
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genetics
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Sertoli Cells
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Spermatogenesis
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genetics
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Spermatozoa
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metabolism
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Testis
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metabolism
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Testosterone
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administration & dosage
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Transcription, Genetic
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Ubiquitin Thiolesterase
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genetics
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metabolism
5.Study on the expression of androgen receptor in testis, epididymis and prostate of adult rats with diabetes.
National Journal of Andrology 2005;11(12):891-894
OBJECTIVETo investigate if there is abnormal expression of androgen receptor (AR) in adult diabetic rats.
METHODSThe diabetic model rats were induced by using streptozotocin (STZ), which were divided into three groups: control (group C), diabetes (group D) and diabetes with insulin replacement group (group ID). The mRNA and protein expressions of androgen receptor in testis, epididymis and prostate were detected by Northern blot and radioimmunoassay, respectively.
RESULTSSerum testosterone levels and AR mRNA in epididymis of group D or Group ID were lower than those of group C (P <0.05) , respectively, and the protein expression of AR in testis and prostate of group D was lower than that of group C (P <0.05).
CONCLUSIONThe expression of androgen receptor decreased in testis, epididymis and prostate of diabetic rats, which weakened the biological effects of AR, and it might be one of the causes that resulted in the sexual and productive dysfunction in diabetic rats.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; Epididymis ; metabolism ; Male ; Prostate ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Androgen ; biosynthesis ; genetics ; Testis ; metabolism
6.Effects of androgen on lipoprotein and the cardiovascular system.
National Journal of Andrology 2007;13(10):928-931
The effects of androgen on lipid and the cardiovascular system are very important. The relationship between androgen and lipoprotein is rather complicated and influenced by many factors. The effects of endogenous androgen on the metabolism of lipoprotein vary with age, environment, nutrition and gender, while the effects of exogenous androgen on lipoprotein vary with different androgen preparations, administration methods and diseases to be treated. Androgen can impact the metabolism of lipoprotein, vascular endothelium, macrophage, vascular smooth muscle, angiotasis, blood coagulation, platelet and so on. The effects of polymorphism of the androgen receptor gene CAG on the cardiovascular system are important and yet somehow controversial and have to be further investigated.
Androgens
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pharmacology
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physiology
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Cardiovascular System
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drug effects
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Female
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Humans
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Lipoproteins
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metabolism
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Male
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Polymorphism, Genetic
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Receptors, Androgen
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genetics
;
physiology
7.The localization and potential function of androgen receptor mRNA in rat submaxillary.
National Journal of Andrology 2003;9(9):681-683
OBJECTIVESTo study the distribution and potential function of androgen receptor (AR) mRNA and AR in rat submaxillary.
METHODSIn situ hybridization using digoxigenin-labled oligonucleotide probes, cell culture and radio-immunoassay were performed to localize the AR and detect the concentration of epidermal growth factor (EGF) in culturing supernant.
RESULTSAR mRNA hybridization signals were detected in glandular epithelial cells of serous acinus and epithelial cells in all gland ducts. The signals distributed in cytoplasma of all positive cells with negative nuclei; Administration of testosterone can significantly increase the level of EGF (P < 0.05).
CONCLUSIONSThe rat submaxillary not only is a target organ of androgen but also can product AR by itself. When androgen combined with androgen receptor and can submaxillary function can be infected and can result in the elevation of the level of EGF secreted.
Animals ; Epidermal Growth Factor ; biosynthesis ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen ; genetics ; physiology ; Submandibular Gland ; metabolism
8.Association of mating type switching/sucrose non-fermenting complex with prostate cancer.
Jun YANG ; Ji-hong LIU ; Ben-yi LI
National Journal of Andrology 2008;14(10):935-938
ATP-dependent chromatin remodeling by the mating type switching/sucrose non-fermenting (SWI/SNF) complex is a basic biological event in the body, which is required for all the key processes involved in DNA metabolism such as gene expression, DNA replication, repair, chromosomal recombination and mitosis. In the past few years, increasing evidence supports a crucial role of this complex in prostate cancer development and progression via multiple ways, such as cell cycle regulation, androgen receptor pathway and DNA methylation. The present paper briefly reviews the recent studies on the association between the SWI/SNF complex and prostate cancer.
Animals
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Cell Cycle Proteins
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DNA Methylation
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Genes, Switch
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Humans
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Male
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Prostatic Neoplasms
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genetics
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metabolism
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Receptors, Androgen
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Sucrose
9.Androgen/androgen receptor directly regulates the expression of Caveolin-1 in mouse epididymides.
Shuang-Gang HU ; Guang-Xin YAO ; Yun SUN
National Journal of Andrology 2013;19(10):867-872
OBJECTIVETo investigate the mechanisms of androgen/androgen receptor (AR) regulating the expression of Caveolin-1 in the mouse epididymis.
METHODSThe AR binding sites associated with the Caveolin-1 gene were identified by searching the database of genomewide AR binding sites in mouse epididymides obtained from chromatin immunoprecipitation-sequencing (ChIP-seq). Total RNA was extracted from the epididymal tissues of normal and castrated mice and those castrated but supplemented with testosterone propionate, and the expression of Caveolin-1 mRNA was detected by RT-PCR and RT-qPCR. ChIP was performed with AR antibodies, and ChIP-PCR and ChIP-qPCR were used to determine the in vivo AR occupancies on the two sites associated with Caveolin-1.
RESULTSTwo AR binding sites associated with Caveolin-1 were found in the database, both located in the second intron region. After castration, the expression of Caveolin-1 was significantly increased, 1.8 +/- 0.17 times that of the control group (P < 0.05), and the fold enrichments of the two AR binding sites were dramatically reduced from 13.5 +/- 1.47 and 10.5 +/- 1.03 to 1.05 +/- 0.17 and 1.4 +/- 0.14, respectively (P < 0.01). After androgen supplement, however, the expression of Caveolin-1 was decreased to normal (P < 0.05), and the fold enrichments of the two AR binding sites significantly increased to 16.4 +/- 2.6 and 10 +/- 0.92, respectively (P < 0.01).
CONCLUSIONCaveolin-1 is a bona fide AR direct target gene in the mouse epididymis, and its expression is negatively regulated by androgen. These findings have provided a new insight into the androgen/AR regulatory network in mouse epididymides.
Androgens ; pharmacology ; Animals ; Binding Sites ; Caveolin 1 ; genetics ; metabolism ; Epididymis ; drug effects ; metabolism ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; genetics ; Receptors, Androgen ; genetics
10.Localization and potential function of androgen receptor in rat salivary gland.
Hong-Jun LI ; Bing YAO ; Wei LIANG ; Yong-Mei WANG ; Qi-Lu XU ; Yu-Feng HUANG
Asian Journal of Andrology 2005;7(3):295-301
AIMTo investigate the localization and quantity of androgen receptor (AR) in the salivary glands of rats with further analysis on the effect of castration.
METHODSSixty male Wistar rats, aged 30-60 days, were randomly divided into three groups (castrated, sham-operated and normal controls) with 20 rats in each group. The rats in the castrated group were castrated and the submaxillary glands were removed after 1 week. The salivary glands of the rats in the sham-operated and the normal control groups were also removed. Parts of the salivary glands were fixed for immunohistochemistry and in situ hybridization assays. Other parts were used for Western blot.
RESULTSAR immunoreactivity in the three groups was localized in the glandular epithelial cells of the serous acinus and the glandular duct of the salivary gland, mainly in the nuclei. AR mRNA hybridization signals in the salivary glands of the castrated group were mainly distributed in the epithelial cells of the convoluted and secretary ducts; AR mRNA in the sham-operated and the normal control groups were found in the epithelial cells of the convoluted, the secretary and the excretory ducts. The quantity of AR in the salivary glands was decreased significantly in the castrated rats compared with the sham-operated and the normal controls. Moreover, epidermal growth factor (EGF) secreted by the salivary glands was also decreased in the castrated rats.
CONCLUSIONCastration appears to affect the production of AR in the salivary gland and the distribution of the AR mRNA and could further affect the function of the salivary gland. The changes of AR and the distribution of AR mRNA may play an important role in the interactions between the testes and the salivary gland.
Animals ; Blotting, Western ; Epidermal Growth Factor ; metabolism ; Immunohistochemistry ; In Situ Hybridization ; Male ; Orchiectomy ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen ; genetics ; metabolism ; physiology ; Salivary Glands ; metabolism