Publications by authors named "Dao-Jun Lv"

8 Publications

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Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer.

Front Cell Dev Biol 2021 25;9:678967. Epub 2021 Jun 25.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 () protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of in PCa and explore the underlying regulatory mechanisms.

Methods: The expression of was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with depletion both and . The expression levels of relevant proteins were detected by Western blotting.

Results: Our finding showed that was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of activated the pathway in PCa cells.

Conclusion: suppresses PCa cell proliferation and metastasis the signaling pathway and is a novel therapeutic target.
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http://dx.doi.org/10.3389/fcell.2021.678967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267926PMC
June 2021

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer.

Cell Death Dis 2021 02 1;12(2):138. Epub 2021 Feb 1.

Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa). SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial-mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.
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http://dx.doi.org/10.1038/s41419-021-03413-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862296PMC
February 2021

Phosphoribosyl pyrophosphate synthetases 2 knockdown inhibits prostate cancer progression by suppressing cell cycle and inducing cell apoptosis.

J Cancer 2020 1;11(5):1027-1037. Epub 2020 Jan 1.

Department of Urology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong Province, China.

Phosphoribosyl pyrophosphate synthetases 2 (PRPS2) protein function as nucleotide synthesis enzyme that plays vital roles in cancer biology. However, the expression profile and function of PRPS2 in prostate cancer (PCa) remain to be identified. Here we investigated the expression of PRPS2 protein in human PCa and paired normal tissues by immunohistochemistry, meanwhile the regulatory effects on cell proliferation, apoptosis and growth of xenograft tumors in nude mice were evaluated in PCa cells with PRPS2 depletion. Moreover, the signaling pathways were also explored by western blot analysis and quantitative polymerase chain reaction assays. We found that PRPS2 was dramatically upregulated in prostate adenocarcinoma tissues in comparison with normal tissues, and that increased PRPS2 was linked intimately to advanced clinical stage and pT status. Functional experiments showed that knockdown of PRPS2 significantly suppressed cell growth both and . In addition, depletion of PRPS2 induced G phase cell cycle arrest and elevated cell apoptosis. Silencing of PRPS2 resulted in the decreased expression of Bcl‑2 and cyclinD1 and increased levels of Bax, cleavage of caspases‑3, caspases‑9 and PARP. Furthermore, we also detected PRPS2 expression was significantly induced after DHT treatment, which implied the important role of PRPS2 in oncogenesis of PCa. Taken together, our findings elucidated that PRPS2 may be a potential novel candidate for PCa therapy.
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http://dx.doi.org/10.7150/jca.37401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959080PMC
January 2020

HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway.

Theranostics 2019 9;9(18):5166-5182. Epub 2019 Jul 9.

Department of Urology, Nanfang Hospital, Southern Medical University/ The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.

: We have previously shown that high-mobility group box 1 () is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of in PCa tumorigenesis. : Gain-of-function and loss-of-function experiments were used to determine the biological functions of both and . Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of and its relationship with Brahma-related gene 1 () was examined by immunohistochemistry. : The results demonstrated that ectopic expression of facilitated growth and metastasis of PCa by enhancing signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of showed the opposite effects. Mechanistically, exerted these functions through its interaction with which may augment function and activate the signaling pathway thereby promoting EMT. Importantly, both and expression was markedly increased in human PCa tissues. : Taken together, these findings indicate that upregulation of promotes PCa development activation of and accelerates metastasis through regulating -mediated EMT. could be used as a novel potential target for the treatment of PCa.
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http://dx.doi.org/10.7150/thno.33972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691575PMC
August 2020

Synthesis and biological evaluation of arylpiperazine derivatives as potential anti-prostate cancer agents.

Bioorg Med Chem 2019 01 22;27(1):133-143. Epub 2018 Nov 22.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

A novel scaffold of arylpiperazine derivatives was discovered as potent androgen receptor (AR) antagonist through rational drug designation based on our pre-work, leading to the discovery of a series of new antiproliferative compounds. Compounds 10, 16, 27, 29 and 31 exhibited relatively strong antagonistic potency against AR and exhibited potent AR binding affinities, while compounds 5, 6, 10, 14, 16, 19, 21, 27 and 31 exhibited strong cytotoxic activities against LNCaP cells (AR-rich) as well as also displayed the higher activities than finasteride toward PC-3 (AR-deficient) and DU145 (AR-deficient). Docking study suggested that the most potent antagonist 16 mainly bind to AR ligand binding pocket (LBP) site through hydrogen bonding interactions. The structure-activity relationship (SAR) of these designed arylpiperazine derivatives was rationally explored and discussed. These results indicated that the novel scaffold compounds demonstrated a step towards the development of novel and improved AR antagonists, and promising candidates for future development were identified.
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http://dx.doi.org/10.1016/j.bmc.2018.11.029DOI Listing
January 2019

Downregulation of lncRNA PVT1 expression inhibits proliferation and migration by regulating p38 expression in prostate cancer.

Oncol Lett 2018 Oct 14;16(4):5160-5166. Epub 2018 Aug 14.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been reported to be overexpressed in prostate cancer cells and associated with tumorigenesis in various types of cancer. However, the biological function of lncRNA PVT1 remains largely unknown. The aim of the present study was to investigate the effect of lncRNA PVT1 expression on the proliferation and migration of prostate cancer cells. Stably transfected prostate cancer cells with downregulated expression of lncRNA PVT1 were constructed by an efficient siRNA fragment, followed by confirmation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was assessed using CCK-8, colony formation and xenograft assays, and cell migration was evaluated using a wound healing assay. The PathScan Intracellular Signaling Array kit was utilized to explore the underlying molecular mechanisms of lncRNA PVT1 expression in prostate cancer cells. RT-qPCR results confirmed that the lncRNA PVT1 expression level was successfully knocked down in prostate cancer cells. When lncRNA PVT1 expression was downregulated in prostate cancer cells, proliferation and migration were significantly inhibited, compared with the control lncRNA PVT1 group. Furthermore, PVT1 knockdown decreased the phosphorylation of p38 in DU145 cells. Therefore, the present study demonstrated that lncRNA PVT1 downregulation inhibits the proliferation and migration of prostate cancer cells, and is associated with p38 phosphorylation.
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http://dx.doi.org/10.3892/ol.2018.9305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144883PMC
October 2018

Suppressed epithelial-mesenchymal transition and cancer stem cell properties mediate the anti-cancer effects of ethyl pyruvate via regulation of the AKT/nuclear factor-κB pathway in prostate cancer cells.

Oncol Lett 2018 Aug 12;16(2):2271-2278. Epub 2018 Jun 12.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Castration-resistant prostate cancer (CRPC) is a leading cause of mortality among cases of prostate cancer (PCa). Current treatment options for CRPC are limited. Ethyl pyruvate (EP), a lipophilic derivative of pyruvic acid, has been reported to have antitumor activities. In the present study, the efficacy of EP against PCa was investigated using two human PCa cell lines and a mouse xenograft tumor model. PC3 and CWR22RV1 cells were treated with EP, and cytotoxicity was evaluated via Cell Counting Kit-8 and colony formation assays, while cell cycle distribution was assessed by flow cytometry. Changes in cell migration and invasion caused by EP treatment were also evaluated with Transwell and wound healing assays, and changes in the expression of intracellular signaling pathway components were detected by western blotting. EP treatment reduced cell viability, induced G1 arrest, and activated the intrinsic apoptosis pathway. Additionally, the experiments revealed that EP administration markedly inhibited tumor growth. EP also reversed epithelial-mesenchymal transition and suppressed cancer stem cell properties in part through negative regulation of AKT/nuclear factor-κB signaling. These results indicate that EP has anticancer activity and , and is therefore a promising therapeutic agent for the treatment of PCa.
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http://dx.doi.org/10.3892/ol.2018.8958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036506PMC
August 2018

Phosphoglycerate mutase 1 knockdown inhibits prostate cancer cell growth, migration, and invasion.

Asian J Androl 2018 Mar-Apr;20(2):178-183

Department of Urology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.

Phosphoglycerate mutase 1 (PGAM1) is upregulated in many cancer types and involved in cell proliferation, migration, invasion, and apoptosis. However, the relationship between PGAM1 and prostate cancer is poorly understood. The present study investigated the changes in PGAM1 expression in prostate cancer tissues compared with normal prostate tissues and examined the cellular function of PGAM1 and its relationship with clinicopathological variables. Immunohistochemistry and Western blotting revealed that PGAM1 expression was upregulated in prostate cancer tissues and cell lines. PGAM1 expression was associated with Gleason score (P = 0.01) and T-stage (P = 0.009). Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. Our results indicate that PGAM1 may play an important role in prostate cancer progression and aggressiveness, and that it might be a valuable marker of poor prognosis and a potential therapeutic target for prostate cancer.
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http://dx.doi.org/10.4103/aja.aja_57_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858104PMC
May 2019
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