Publications by authors named "Zilian Cui"

17 Publications

  • Page 1 of 1

LncRNA PlncRNA-1 accelerates the progression of prostate cancer by regulating PTEN/Akt axis.

Aging (Albany NY) 2021 Apr 13;13(8):12113-12128. Epub 2021 Apr 13.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Long non-coding RNAs are key regulators of tumor development and progression, with the potential to be biomarkers of tumors. This study aimed to explore the role of PlncRNA-1 in the progression of prostate cancer (PCa). We found that PlncRNA-1 was up-regulated in 85.29% of PCa tissues and could predict the T stage of PCa patients to a certain extent. Results showed that inhibition of PlncRNA-1 expression potentially promoted cell apoptosis, suppressed the proliferation, migration, and invasion of cells, and triggered G2/M cycle arrest and . PlncRNA-1 was mainly localized in the nucleus and PlncRNA-1 expression and phosphatase and tensin homologue (PTEN) expression were negatively correlated. Mechanistically, knockdown of PlncRNA-1 increased expression levels of PTEN protein and phosphorylated PTEN protein, and decreased expression levels of Akt protein and phosphorylated Akt protein. Rescue experiments demonstrated that PTEN inhibitors abolished the changes in PTEN/Akt pathway caused by PlncRNA-1 interference. PlncRNA-1 can promote the occurrence and development of PCa via the PTEN/Akt pathway. PlncRNA-1 may, therefore, be a new candidate target for the treatment of PCa.
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http://dx.doi.org/10.18632/aging.202919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109094PMC
April 2021

Corrigendum to "The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma".

Biomed Res Int 2020 10;2020:1025178. Epub 2020 Dec 10.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250000, China.

[This corrects the article DOI: 10.1155/2020/1932948.].
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http://dx.doi.org/10.1155/2020/1025178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749763PMC
December 2020

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis.

Cell Death Dis 2020 12 7;11(12):1038. Epub 2020 Dec 7.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.

Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial-mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.
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http://dx.doi.org/10.1038/s41419-020-03240-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721747PMC
December 2020

The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.

Biomed Res Int 2020 1;2020:1932948. Epub 2020 May 1.

Department of Urology, Shandong Province Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250000, China.

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.
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http://dx.doi.org/10.1155/2020/1932948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212275PMC
March 2021

Crossed-fused renal ectopia with renal calculi: Two case reports and a review of the literature.

Medicine (Baltimore) 2019 Nov;98(48):e18165

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Rationale: Crossed renal ectopia (CRE) is a rare congenital anomaly that is frequently associated with gastrointestinal, cardiovascular, genital and bone malformations. To the best of our knowledge, only 35 cases of crossed renal ectopia involving calculi and 30 cases of CRE associated with renal carcinoma have been reported to date.

Patient Concerns: Here, we present 2 cases of crossed renal ectopia. A 59-year-old woman with diabetes presented to our hospital with abdominal pain. The second patient was a 24-year-old woman who complained with abdominal pain with a duration of 1 day.

Diagnoses: On the basis of abdominal ultrasonography, we suspected a solitary kidney both in the two patients. Combined with retrograde pyelography and 3D computed tomography, case 1 was diagnosed as an S-shaped right-to-left crossed-fused ectopic kidney with many stones in the left (normal) renal pelvis and case 2 was confirmed to have lump right-to-left crossed-fused renal ectopia with two 3-mm stones in the renal pelvis of the 2 kidneys.

Interventions: Case 1 underwent percutaneous nephrolithotomy while case 2 refused to undergo surgery and underwent conservative treatment for pain relief.

Outcomes: Two patients have been followed up and have no stones recurrence.

Lessons: Crossed fused renal ectopia is easily misdiagnosed as a solitary kidney. CRE is so rare that the recognition of the disease needs to be improved and effective treatment should be taken timely. According to the two cases and literature review, minimally invasive surgery has become increasingly common to treat CRE with stones and carcinoma.
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http://dx.doi.org/10.1097/MD.0000000000018165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890333PMC
November 2019

Abdominal cocoon with bilateral cryptorchidism and seminoma in the right testis: a case report and review of literature.

BMC Surg 2019 Nov 11;19(1):167. Epub 2019 Nov 11.

Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.

Background: Abdominal cocoon is a rare peritoneal lesion and is difficult to diagnose because of its lack of special clinical manifestations. Until now, there is no case report of abdominal cocoon combined with cryptorchidism and seminoma.

Case Presentation: A case of abdominal cocoon with cryptorchidism and seminoma was diagnosed and treated in our hospital. The patient had no symptoms except occasional abdominal pain. He underwent laparoscopy because of bilateral cryptorchidism and seminoma in the right testis. During the surgery, he was diagnosed with abdominal cocoon due to the thick fibrous tissues which was tightly adhered and encased part of intestine like a cocoon. Enterolysis and bilateral cryptochiectomy were performed after the diagnosis and nutritional and symptomatic support was provided after the surgery. The patient recovered well and was discharged soon. The postoperative pathological examination confirmed the presence of bilateral cryptorchidism and seminoma in the patient's right testis.

Conclusion: There are only a handful of cases where a patient has both abdominal cocoon and cryptorchidism. Since the etiologies of both diseases remain unknown, further research is required to investigate effective diagnosis and treatment for the diseases and explore the potential connection between the two diseases.
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http://dx.doi.org/10.1186/s12893-019-0636-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849259PMC
November 2019

Correction: Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer.

Oncotarget 2019 Aug 27;10(50):5253. Epub 2019 Aug 27.

Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

[This corrects the article DOI: 10.18632/oncotarget.15318.].
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http://dx.doi.org/10.18632/oncotarget.27174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718261PMC
August 2019

KMT2D inhibits the growth and metastasis of bladder Cancer cells by maintaining the tumor suppressor genes.

Biomed Pharmacother 2019 Jul 14;115:108924. Epub 2019 May 14.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, China. Electronic address:

KMT2D, a kind of histone H3 lysine 4 (H3K4) methyltransferase, its abnormal expression confirmed to be associated with diverse tumors, but is lack of defined role in bladder cancer (BC). KMT2D mutation was analyzed using several databases. Immunohistochemistry and clinicopathological analysis of KMT2D in 51 paired of BC tissues and corresponding normal tissues were used to evaluate the relationship between KMT2D and BC. The effects of silencing or over-expressing KMT2D on HTB-9 and T24 cell viability, migration and invasion were performed using MTT, wound scratch and Transwell, respectively. Also, bladder cancer mouse model was established by hypodermic injection of the BC cells. Associated expressions of methylation genes, oncogenes and tumor suppressors were assessed by western blot and quantitative real-time PCR. KMT2D was frequent mutation in various tumors, including BC. It was negative expression in BC tissues and cells, also implicated with tumor stages and lymph node metastasis. In silencing KMT2D HTB-9 and T24 cells, cell viability, migration and invasion were notably promoted. Meanwhile, knockdown of KMT2D benefited to solid tumor formation in vivo. However, over-expressing KMT2D represented contrary results. Especially, KMT2D over-expression induced the activity of H3K4 monomethylation (me1), and effectively enhanced PTEN and p53 expressions as well as repressed STAG2 expression. Meanwhile, KMT2D had no obvious effect on Survivin. This work suggested an anti-tumor role for KMT2D in vitro and in vivo, as well as provided a possible tumor inhibition mechanism in which KMT2D enhanced H3K4me1 activity to support the expressions of tumor suppressors.
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http://dx.doi.org/10.1016/j.biopha.2019.108924DOI Listing
July 2019

HUWE1 upregulation has tumor suppressive effect in human prostate cancer cell lines through c-Myc.

Biomed Pharmacother 2018 Oct 11;106:309-315. Epub 2018 Jul 11.

Department of Urology, Chinese PLA 252 Hospital, Baoding, 071000, China. Electronic address:

Purpose: We investigated the regulatory function of HECT, UBA and WWE domain-containing protein 1, E3 ubiquitin protein ligase (HUWE1) in human prostate cancer (CaP).

Methods: HUWE1 was overexpressed (through transfection) or downregulated (through lentiviral transduction) in CaP cell lines, PC3 and DU145 cells. The functions of HUWE1 overexpression or downregulation on CaP cancer cell proliferation, migrationin vitro, and explant in vivo were examined. In addition, the regulatory effect of HUWE1 on c-Myc expression was assessed. In HUWE1-overexpressed CaP cells, c-Myc was further upregulated to assess whether c-Myc was directly involved in HUWE1-induced regulation in CaP.

Results: HUWE1 overexpression inhibited CaP proliferation and migrationin vitro, and explant growth in vivo. On the other hand, HUWE1 downregulation had no effects on CaP in vitro. C-Myc was downregulated in HUWE1-overexpressed, but un-changed in HUWE1-downregulated, CaP cells. Further upregulating c-Myc in HUWE1-overexpressed CaP cells reversed the tumor-suppressing effects by HUWE1-overexpression on cancer proliferation and migration in vitro.

Conclusion: HUWE1 overexpression could functionally suppress CaP development bothin vitro and in vivo, possibly by inverse regulation on c-Myc.
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http://dx.doi.org/10.1016/j.biopha.2018.06.058DOI Listing
October 2018

Utility of fluorescence hybridization analysis for detecting upper urinary tract-urothelial carcinoma.

J Cancer Res Ther 2017 ;13(4):647-650

Minimally Invasive Urology Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.

Objectives: The objective of this study was to evaluate the clinical utility of fluorescence in situ hybridization (FISH) in the detection of upper urinary tract-urothelial carcinoma (UUT-UC).

Methods: Between November 2011 and November 2015, voided urine specimens from 52 consecutive patients with UUT-UC and 26 controls were collected for both FISH test and cytology. Sensitivity and specificity of FISH test and cytology were determined and compared. The frequency of chromosomal aberrations was also analyzed.

Results: For FISH analysis, the sensitivity was 79.5% and specificity was 96.3%. For cytology, the sensitivity was 27.3% and specificity was 100%. The overall sensitivity for FISH was significantly higher than that of in single value-based urine cytology (79.5% vs. 27.3%, respectively, P < 0.001). The sensitivities of FISH and cytology by grade were 64.3% vs. 28.6% for low-grade urothelial carcinomas (P = 0.128) and 86.7% vs. 26.7% for high-grade urothelial carcinomas (P < 0.001), respectively. Twenty-seven (77.1%) cases were positive due to the gain of two or more chromosomes in five or more urinary cells, among which, 21 (60%) cases showed positivity in all the 4 chromosomes, 7 (20%) cases matched the criterion that 10 or more cells gained a single chromosome, whereas only 1 (2.9%) case was positive because of the homozygous deletion of 9p21 in 12 or more cells.

Conclusions: FISH has superior sensitivity and similar specificity in the detection of UUT-UC, compared with cytology. The present findings indicated that FISH can be applied as a noninvasive diagnostic tool for suspected UUT-UC patients.
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http://dx.doi.org/10.4103/jcrt.JCRT_74_17DOI Listing
May 2018

Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer.

Oncotarget 2017 Apr;8(16):26090-26099

Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: To confirm that PlncRNA-1 regulates the cell cycle in prostate cancer cells and induces epithelial-mesenchymal transition (EMT) in prostate cancer through the TGF-β1 pathway.

Results: PlncRNA-1 and TGF-β1 expression levels were significantly higher in prostate cancer tissues than in normal prostate tissues (P < 0.05) and were significantly positively correlated. TGF-β1, N-cadherin and Cyclin-D1 were downregulated and E-Cadherin was upregulated in LNCAP cells after silencing of PlncRNA-1, as determined by real-time PCR and Western blot. TGF-β1, N-cadherin and Cyclin-D1 were upregulated and E-cadherin was downregulated in C4-2 cells, as determined by real-time PCR and Western blot. Overexpression of PlncRNA-1 in C4-2 cells was observed when TGF-β1 inhibitor LY2109761 was added. Western blot analysis showed that compared with their expression when TGF-β1 inhibitor LY2109761 was not added, N-Cadherin and CyclinD1 expression decreased and E-Cadherin expression increased. Transwell results showed that the invasive ability of C4-2 cells was enhanced after overexpression of PlncRNA-1, and the invasion ability was decreased after addition of TGF-β1 inhibitor LY2109761. The cell cycle was blocked by overexpression of PlncRNA-1 in C4-2 and by the addition of TGF-β1 inhibitor LY2109761, as determined by flow cytometry. In vitro experiments showed that PlncRNA-1 can regulate the growth of prostate cancer cells and EMT through the TGF-β1 pathway. In vivo experiments also confirmed the above results. Tumor growth was significantly blocked by overexpressing PlncRNA-1 in C4-2 cells and by the TGF-β1 inhibitor LY2109761 in animal experiments.

Materials And Methods: The expression levels of PlncRNA-1 and TGF-β1 were analyzed in 19 prostate cancer tissue samples and in adjacent normal tissue samples, 4 Pca cell lines, including LNCaP, C4-2,DU145, and PC3, and 1 normal prostate epithelial cell line RWPE-1. LNCAP cells were divided into the LNCAP control group and the LNCAP-PlncRNA-1-siRNA group. Cells from the prostate cancer cell line C4-2 were divided into the C4-2 control group and the C4-2-PlncRNA-1 experimental group. Changes in TGF-β1, E-cadherin and N-cadherin were detected by qPCR and Western Blot assay after silencing and overexpression of PlncRNA-1. The cell cycle, cell invasion, and levels of Cyclin-D1, E-Cadherin, and N-Cadherin were observed after adding TGF-β1 inhibitor LY2109761 in the C4-2-PlncRNA-1 group. The effects of TGF-β1 inhibitor LY2109761 on the tumorigenicity of C4-2 cells after overexpression of PlncRNA-1 was investigated in vivo.

Conclusions: PlncRNA-1 is an oncogene that regulates the cell cycle, cyclin-D1 and EMT in prostate cancer cells through the TGF-β1 pathway.
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http://dx.doi.org/10.18632/oncotarget.15318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432240PMC
April 2017

Narrow band imaging-assisted transurethral resection reduces the recurrence risk of non-muscle invasive bladder cancer: A systematic review and meta-analysis.

Oncotarget 2017 Apr;8(14):23880-23890

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Context: Compared with white light imaging (WLI) cystoscopy, narrow band imaging (NBI) cystoscopy could increase the visualization and detection of bladder cancer (BC) at the time of transurethral resection (TUR). NBI cystoscopy could increase the detection of BC, but it remains unclear whether narrow band imaging-assisted transurethral resection (NBI-TUR) could reduce the recurrence risk of non-muscle invasive bladder cancer (NMIBC). Several randomized clinical trials (RCTs) have recently tested the efficacy of NBI-TUR for NMIBC.

Objective: To perform a systematic review and meta-analysis of RCTs and evaluate the efficacy of NBI-TUR for NMIBC compared with white light imaging-assisted transurethral resection (WLI-TUR). The end point was recurrence risk.

Evidence Acquisition: A systematic review of PubMed, Medline, Ovid, Embase, Cochrane and Web of Science was performed in February 2016 and updated in July 2016.

Evidence Synthesis: Overall, six (n = 1084) of 278 trials were included. Three trials performed narrow band imaging-assisted electro-transurethral resection (NBI-ETUR), and two trials performed narrow band imaging-associated bipolar plasma vaporization (NBI-BPV). The last trial performed narrow band imaging-associated holmium laser resection (NBI-HLR). Statistical analysis was performed using Review Manager software (RevMan v.5.3; The Nordic Cochrane Center, Copenhagen, Denmark). The recurrence risk was compared by calculating risk ratios (RRs) with 95% confidence interval (CIs). Risk ratios with 95% CIs were calculated to compare 3-mo, 1-yr, and 2-yr survival rates. NBI-TUR was associated with improvements in the 3-mo recurrence risk (RR: 0.39; 95% CI, 0.26-0.60; p < 0.0001), 1-yr recurrence risk (RR: 0.52; 95% CI, 0.40-0.67; p < 0.00001) and 2-yr recurrence risk (RR: 0.60; 95% CI, 0.42-0.85; p = 0.004) compared with WLI-TUR.

Conclusions: Compared with WLI-TUR, NBI-TUR can reduce the recurrence risk of NMIBC. The results of this review will facilitate the appropriate application of NBI in NMIBC.
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http://dx.doi.org/10.18632/oncotarget.13054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410352PMC
April 2017

Calcifying Fibrous Tumor of the Tunica Vaginalis Testis: A Report of 2 Cases.

Urology 2017 Feb 28;100:e9-e13. Epub 2016 Sep 28.

Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.

Objective: To improve the clinical diagnosis and treatment of calcifying fibrous tumor (CFT) of the tunica vaginalis testis, we discussed clinical manifestations and pathologic features of CFT.

Materials And Methods: A retrospective analysis of 2 cases of CFT that occurred in our hospital was performed, and we also reviewed the literature and research reports.

Results: Both patients underwent local excision with testis preservation surgery, and pathology examination confirmed the presence of multiple CFTs of the tunica vaginalis testis.

Conclusion: CFTs are rare, benign multiple lesions, and the recognition of which needs to be improved to avoid overtreatment. We are the first to describe 2 cases of CFT combined with hepatitis B, but additional studies are needed to confirm the relationship between these conditions.
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http://dx.doi.org/10.1016/j.urology.2016.09.022DOI Listing
February 2017

Oncogenic CUL4A determines the response to thalidomide treatment in prostate cancer.

J Mol Med (Berl) 2012 Oct 16;90(10):1121-32. Epub 2012 Mar 16.

Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, No. 168, Changhai Rd, Yangpu District, Shanghai, 200433, China.

Thalidomide is experimentally used to treat various human cancers; however, clinical responses to thalidomide are sporadic. Here we demonstrate that CUL4A plays an oncogenic role in prostate cancer development and prostate cancer cells with higher level of CUL4A are particularly sensitive to thalidomide treatment. We show that CUL4A is frequently overexpressed in human primary prostate cancer and cell lines. Notably, subjects with tumors that highly expressed CUL4A had poor overall survival. CUL4A downregulation inhibited cell proliferation and induced apoptosis in vitro and in vivo, whereas CUL4A overexpression transformed human normal prostate epithelial cells and promoted invasion, which was attenuated by the extracellular signal-regulated kinase (ERK) inhibitor. We further show that the sensitivity to thalidomide is positively correlated with CUL4A expression in a panel of prostate cell lines. Ectopic CUL4A expression greatly enhanced sensitivity to thalidomide, while its downregulation conferred resistance to this drug. Mechanistically, thalidomide decreased CUL4A in a time- and dose-dependent manner, consequently leading to inaction of ERK pathway. Finally, we show that cereblon level is correlated with CUL4A expression and downregulated in thalidomide-resistant prostate cancer cell. Our results offer the first evidence that CUL4A is a potential therapeutic target for prostate cancer and may serve as a biomarker for assessing prognosis of human prostate cancer and response to thalidomide treatment.
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http://dx.doi.org/10.1007/s00109-012-0885-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650856PMC
October 2012

RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.

Cell Res 2012 May 21;22(5):806-21. Epub 2012 Feb 21.

Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

There are remarkable disparities among patients of different races with prostate cancer; however, the mechanism underlying this difference remains unclear. Here, we present a comprehensive landscape of the transcriptome profiles of 14 primary prostate cancers and their paired normal counterparts from the Chinese population using RNA-seq, revealing tremendous diversity across prostate cancer transcriptomes with respect to gene fusions, long noncoding RNAs (long ncRNA), alternative splicing and somatic mutations. Three of the 14 tumors (21.4%) harbored a TMPRSS2-ERG fusion, and the low prevalence of this fusion in Chinese patients was further confirmed in an additional tumor set (10/54=18.5%). Notably, two novel gene fusions, CTAGE5-KHDRBS3 (20/54=37%) and USP9Y-TTTY15 (19/54=35.2%), occurred frequently in our patient cohort. Further systematic transcriptional profiling identified numerous long ncRNAs that were differentially expressed in the tumors. An analysis of the correlation between expression of long ncRNA and genes suggested that long ncRNAs may have functions beyond transcriptional regulation. This study yielded new insights into the pathogenesis of prostate cancer in the Chinese population.
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http://dx.doi.org/10.1038/cr.2012.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343650PMC
May 2012

The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor.

Urol Oncol 2013 Oct 20;31(7):1117-23. Epub 2012 Jan 20.

Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

Objective: Emerging evidences implicate long noncoding RNAs (lncRNAs) are deregulated in cancer development. The purpose of the current study is to investigate the role of new lncRNA, named PlncRNA-1, in prostate cancer (CaP) pathogenesis.

Materials And Methods: In this study, real-time q-PCR was used to demonstrate the expression of PlncRNA-1 in 16 pairs CaP tissues and matched normal tissues, 14 pairs CaP tissues and BPH tissues, 4 CaP cell lines, including LNCaP, LNCaP-AI, PC3, and C4-2, and 2 normal prostate epithelial cell lines RWPE-1 and PWR-1E. After PlncRNA-1 was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, cell proliferation and apoptosis were assessed using CCK-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). After PlncRNA-1 and AR was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, real-time q-PCR and Western blotting were used to measure reciprocal regulation of PlncRNA-1 and AR.

Results: We showed that expression PlncRNA-1, was significantly higher in CaP cells relative to normal prostate epithelial cells, as well as higher in human CaPs compared with normal tissues and benign prostatic hyperplasia (BPH). Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI. Mechanistically, PlncRNA-1 suppression by siRNA resulted in a decrease of androgen receptor (AR) mRNA, protein and AR downstream target. Of note, blockade of AR signaling with siRNA also resulted in a suppression of PlncRNA-1 expression in CaP cell lines.

Conclusions: Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target.
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http://dx.doi.org/10.1016/j.urolonc.2011.11.030DOI Listing
October 2013