Open Access

High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway

  • Authors:
    • Weiguo Chen
    • Peng Zhou
    • Xiaowei Li
  • View Affiliations

  • Published online on: April 25, 2016     https://doi.org/10.3892/ijmm.2016.2575
  • Pages: 1551-1557
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

DEAD (Asp-Glu-Ala-Asp) box polypeptide 20 (DDX20), a member of the DEAD box protein family, encodes an RNA helicase. Previous research has revealed that DDX20 may act as a tumor suppressor in hepatocellular carcinoma and as a tumor promoter in breast cancer. These conflicting reports prompted us to explore the role of DDX20 in prostate cancer (PCa). To gain insight into the functions of DDX20 in PCa, we examined DDX20 expression patterns in a PCa tissue microarray with 99 PCa tissue samples. The results of immunohistochemical staining revealed that DDX20 expression is frequently upregulated in PCa tissues compared with that in the adjacent tissues and further clinicopathological analysis showed that the expression level of DDX20 closely correlates with tumor size, TNM stage (positive correlation) and patient prognosis (negative correlation). Both gain‑of- and loss‑of‑function assays were performed in vitro; the overexpression of DDX20 enhanced the proliferation and metastatic potential of cancer cells and this was examined by performing a cell counting kit-8 (CCK-8) assay, wound healing assay and Transwell migration assay. Furthermore, we found that there is a positive correlation between the expression of matrix metallopeptidase 9 (MMP9) and DDX20 expression. These findings led us to examine whether DDX20 may exert effects through the NF‑κB pathway. Luciferase reporter assays suggested that DDX20 altered the activity of NF-κB. Taken together, these findings show that DDX20 may promote the progression of PCa through the NF-κB pathway.

Introduction

Prostate cancer (PCa) is the second most frequently diagnosed cancer in Europe (1) and the second leading cause of cancer mortality in males in the USA (2). Although a complete understanding of the causes of PCa remains elusive, obesity, advancing age and family history have been established as the principal risk factors (3). Genetic alterations may also increase the risk of developing PCa, as suggested by associations with specific gene variants. Mutations in BRCA1 and BRCA2 (4), hereditary PCa gene 1, the androgen receptor and the vitamin D receptor (5), as well as fusion between TMPRSS2 and ETS family members, have also been implicated in PCa (6). Despite recent advances, the molecular mechanisms involved in the development and progression of PCa remain unclear.

DEAD (Asp-Glu-Ala-Asp) box polypeptide 20 (DDX20), a member of the DEAD box protein family, encodes an RNA helicase. Recently, the roles of DDX20 have been reported in hepatocellular carcinoma (HCC) (7) and breast cancer (8). In HCC, a deficiency of DDX20 was demonstrated to impair the functioning of miRNA-140 and lead to hepatocarcinogenesis. However, in breast cancer, DDX20 was identified as a biomarker and an oncogenic driver of metastasis. These contradictory findings prompted us to explore the role of DDX20 in PCa.

In the present study, we demonstrated that the expression of DDX20 is frequently increased in PCa. As DDX20 is reportedly associated with the metastasis of breast cancer, we examined whether DDX20 affects the same biological activities in PCa. The results of the present study indicate that DDX20 plays a similar role in PCa.

Materials and methods

Patients and sample collection

Twenty-four patients with PCa, who underwent surgical resection at Chengdu Military General Hospital (Chengdu, China) between 2008 and 2014, were enrolled into the present study. All samples were frozen in liquid nitrogen immediately following surgical resection and stored at −80°C until RNA extraction.

Ethics statement

All fresh tumor tissues and matched adjacent tissues were collected from patients with pathologically and clinically confirmed PCa. All human tumor tissues were obtained with written informed consent from patients. The Institutional Review Board of Chengdu Military General Hospital approved the use of the tumor sample in this study.

Immunohistochemistry (IHC)

A PCa tissue microarray (TMA; HPro-Ade180PG-01) containing tissues from 99 cases (81 paired carcinoma and adjacent tissues as well as 18 cancer specimens) was purchased from Outdo Biotech (Shanghai, China). Staining of the TMA was performed according to standard IHC protocols. Following deparaffinization and dehydration of the TMA, endogenous peroxidase activity was blocked with 0.3% hydrogen peroxide (Sangon, Shanghai, China) at 37°C for 30 min, and then antigen retrieval was performed by boiling in 10 mM citrate buffer (pH 6.0) for 15 min. The sections were blocked with 10% bovine serum albumin (BSA; Sangon) for 1 h and incubated with DDX20 antibody (1:1,000; 11324-1-AP) and matrix metallopeptidase 9 (MMP9) antibody (1:1,000; 10375-2-AP) (both from ProteinTech, Chicago, IL, USA) overnight at 4°C. The next day, the TMA was incubated with horseradish peroxidase (HRP)-labeled anti-mouse secondary antibody (1:200; Dako, Carpinteria, CA, USA) for 1 h at room temperature. Antibody binding was detected using 3,3′-diaminobenzidine (DAB) in substrate chromogen solution (Dako). The TMA was counterstained with hematoxylin (Beyotime, Nantong, China) prior to dehydration and mounting. The final expression level of DDX20 was designated as a low and high expression group: score 0–1, low expression; 2–3, high expression. DDX20 expression was quantified by two independent pathologists. The slides were visualized using a Primostar FL2 microscope (Carl Zeiss, Oberkochen, Germany).

Cell culture

The PCa cell lines LNCaP, PC-3 and DU145 were obtained from the American Type Culture Collection (ATCC; Manassas, VA, USA). All of the cell lines were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 IU/ml penicillin and 100 µg/ml streptomycin (all from Gibco, Carlsbad, CA, USA) at 37°C in a 5% humidified CO2 atmosphere.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)

The surgical specimens were homogenized using a Mixer Mill MM 300 homogenizer (Qiagen, Chatsworth, CA, USA). Total RNA from these tissues and the PCa cell lines was then isolated using TRIzol reagent (Takara Bio, Inc., Otsu, Japan) and reverse transcribed using the PrimeScript RT-PCR kit (Takara Bio, Inc.) according to the manufacturer's instructions. Target gene expression was determined by performing qPCR with a SYBR Premix Ex Taq kit (Takara Bio, Inc.) and an ABI 7500 real-time PCR system (Applied Biosystems, Foster City, CA, USA). The primers for qPCR were designed as follows: DDX20 forward, 5′-CCGGGGAGAGGAAGAAA ATA-3′ and reverse, 5′-ACTTCCACATCCCAATCCAC-3′; MMP9 forward, 5′-ACGACGTCTTCCAGTACCGA-3′ and reverse, 5′-GCACTGCAGGATGTCATAGG-3′; and GAPDH forward, 5′-GGAGCGAGATCCCTCCAAAAT-3′ and reverse, 5′-GGCTGTTGTCATACTTCTCATGG-3′. GAPDH was amplified as an internal control. We performed the assays according to the following program: 95°C for 30 sec, followed by 40 cycles at 95°C for 5 sec and 60°C for 31 sec, and finally 95°C for 15 sec, 60°C for 1 min and 95°C for 15 sec. The relative expression of DDX20 and MMP9 was calculated using the 2−ΔΔCT method with 18S RNA as the control.

DDX20 RNA interference (RNAi)

Specific small interfering RNAs (siRNAs; GenePharma, Shanghai, China) were designed to silence DDX20 and for the purpose of avoiding off-target effects, we used an siRNA pool which contained three siRNAs. The DU145 and the PC-3 cells were seeded at at a density of 30×104 cells in a final volume of 1.5 ml in 6-well plates. Pooled siRNAs were transfected at a final concentration of 10 nM with Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA). The sequences for the DDX20 siRNAs were as follows: siNC, 5′-UUCUCCGAACGUGUCACGUTT-3′; si-1, 5′-TCTTTATTCTTGATGAA-3′; si-2, 5′-GTGGATGATCGTATTT-3′ and si-3, 5′-GTATTACAAAGTTGTCAA-3′.

Ectopic expression of DDX20

The expression plasmid containing the open reading frame of DDX20 and empty vector was purchased from GeneCopoeia (Guangzhou, China). The LNCaP cells (30×104 cells) were seeded in a 6-well plate and transfected with 2 µg plasmid using Lipofectamine 2000 (Invitrogen). After a 48 h incubation, stably transfected cells were selected using 1 mg/ml G418 (Gibco) in DMEM and grown for 2 weeks. The G418-resistant colonies were isolated by a limited dilution approach. They were expanded and then maintained in regular growth medium containing 1 mg/ml G418.

Western blot analysis

The total protein was extracted using RIPA lysis buffer (Beyotime, Haimen, China) according to the manufacturer's instructions and 50 µg protein was separated by reducing SDS-PAGE, and transferred onto a nitrocellulose membrane. The membrane was then blocked in TBS buffer containing 5% BSA (Sangon) for 1 h. The membrane was incubated with primary antibodies for DDX20 (1:1,000; 11324-1-AP); MMP9 (1:1,000; 10375-2-AP), and GAPDH (1:5,000; 10494-1-AP, all from ProteinTech) overnight, and then followed by HRP-linked secondary antibody (#7074; Cell Signaling Technology, Danvers, MA, USA). Immobilon™ Western Chemiluminescent HRP Substrate kit (Millipore Corp, Darmstadt, Germany) was used for detection.

Cell counting kit-8 (CCK-8) assay of cell viability

To evaluate changes in cell viability, CCK-8 assays were performed. The transfected cancer cells were seeded at a density of 4×104 cells/well in 96-well plates at a final volume of 100 µl medium/well. Cell viability was quantified by adding 10 µl CCK-8 (Dojindo, Kumamoto, Japan). After a 1.5 h incubation, the plates were monitored at specific time points using a PowerWave XS Microplate reader (BioTek, Winooski, VT, USA), which measured absorbance at 450 nm.

Wound healing assay

The transfected cancer cells were seeded onto 12-well plates and cultured until confluent. Wounds were generated using a sterile 200 µl pipette tip (Axygen, Union City, CA, USA). The cells were then cultured for an additional 72 h. Wound closure was assessed using an IX71 inverted microscope (Olympus Corp., Tokyo, Japan). The cell migration distance was measured using Adobe Illustrator CS5 software and compared with baseline measurements. Each experiment was performed in triplicate.

Invasion assay

For the Transwell migration assay, the transfected cells (4×104) were placed in the top chamber of each insert chamber (Millipore Corp.) with the Matrigel-coated membrane. The cells were trypsinized and resuspended in serum-free DMEM and 700 µl complete medium was injected into the lower chamber. The plates were incubated for 48–72 h, and then the medium and the cells remaining in the top chambers were removed. After fixation and staining with 0.1% crystal violet (Beyotime, Nantong, China), the cells that had migrated to the lower membrane of the inserts were counted and images were captured under an IX71 inverted microscope (Olympus Corp.).

Luciferase reporter assays

To perform luciferase reporter assays, the transfected cells were seeded in 96-well plates and transfected with a mixture of 100 ng NF-κB reporter plasmids and 10 ng Renilla (Promega, Madison, WI, USA) according to the manufacturer's instructions for the Lipofectamine 2000 transfection system. Following 48 h of incubation, firefly and Renilla luciferase activities were measured sequentially in the cell lysates using the Dual-Luciferase Reporter Assay system (Promega).

Statistical analysis

Statistical analysis was conducted using SPSS 16.0 software (SPSS, Inc., Chicago, IL, USA). We performed Chi-square tests using cross-tabulation analysis in order to assess the relationships between the expression levels of DDX20 and clinicopathological factors. Overall survival (OS) was calculated using the Kaplan-Meier method. The survival distributions were compared through the log-rank test. The Student's t-test was used for comparisons between groups. A P-value <0.05 was considered to indicate a statistically significant difference.

Results

Expression of DDX20 is significantly upregulated in PCa

Recently, a study showed that DDX20 was highly expressed in human breast cancer and is associated with tumor metastasis (8). This prompted us to explore the functions of DDX20 in PCa. A query of the Oncomine database revealed that notably DDX20 gene expression is significantly upregulated in PCa tissue compared with that in normal prostate gland tissue (Fig. 1A). To further delineate the expression profile of DDX20 in fresh PCa and adjacent tissues, we examined the mRNA levels of DDX20 in 24 paired adjacent and malignant tissues. As shown in Fig. 1B, the mRNA expression of DDX20 was significantly increased in the carcinomas compared with that in the adjacent tissues. Furthermore, we detected DDX20 in a TMA which contained 99 malignant tissues and 81 non-malignant adjacent tissues. We found that DDX20 was more commonly detected in the malignant tissues, as shown in Fig. 1C and this was indicated by stronger DDX20 staining in the carcinoma tissues than in the adjacent tissues. We then analyzed the correlation between DDX20 expression and patient prognosis and found that the patients with high DDX20 expression had lower OS (P=0.024) (Fig. 1D). The analysis of the correlation between DDX20 expression and key clinicopathological features is presented in Table I and shows that DDX20 expression is associated with tumor size, local infiltration and Gleason grade.

Table I

Correlation between DDX20 expression and key clinicopathological features.

Table I

Correlation between DDX20 expression and key clinicopathological features.

VariableDDX20 (n=99)
LowHighP-value
Age (years)
 ≤5034130.183
 >503121
Tumor size (cm)
 ≤528280.014a
 >51132
Local infiltration
 Yes3630.041a
 No627
Gleason grade
 I210.018a
 II–III1040
 IV–V442

a P<0.05.

Human PCa cell lines express DDX20

The significant correlation between DDX20 expression and clinicopathological features prompted us to investigate the effect of DDX20 on various cellular functions during PCa development. Firstly, we examined the expression of DDX20 using RT-qPCR; the DU145 and PC-3 cells exhibited higher expression levels of DDX20 compared with the LNCaP cells (Fig. 2A). To confirm the protein expression of DDX20 in the three cell lines, we performed western blot analysis and the results showed the same pattern as the RT-qPCR results (Fig. 2B).

DDX20 contributes to the proliferation, migration and invasiveness of human PCa cells

We selected the DU145 and PC-3 cell lines for further RNAi analysis and the LNCaP cell line for use in overexpression experiments in order to examine DDX20 expression. The transfection of the DU145 and PC-3 cells with DDX20 siRNA reduced DDX20 expression (Fig. 3A). We studied various cellular functions, namely proliferation, migration and invasion, following siRNA treatment. To examine cell proliferation, we performed CCK-8 cell viability assays and found that cell viability decreased significantly in the DDX20- silenced cells (Fig. 3B). We then assessed cell migratory behavior. After silencing DDX20, we performed wound-healing assays and found that DDX20 depletion led to decreased migration (Fig. 3C and D). Given that the suppression of DDX20 affects cell motility, we next explored the effects of decreasing DDX20 expression on the invasiveness of the malignant cells by performing the Matrigel-coated Transwell invasion assay. In the DU145 and PC-3 cells, knockdown of DDX20 resulted in 40–50% fewer cells invading through the Matrigel-coated inserts (Fig. 3E and F). Taken together, these results demonstrate that DDX20 depletion led to the inhibition of cell proliferation, migration and invasion.

Ectopic expression of DDX20 contributes to cell proliferation, migration and invasiveness

To further substantiate our findings, we then evaluated whether the ectopic expression of DDX20 had the potential to adversely affect LNCaP cells. We found that the ectopic expression of DDX20 markedly elevated the expression of DDX20 (Fig. 4A). The ectopic expression of DDX20 increased LNcaP cell viability (Fig. 4B). In addition, the ectopic expression of DDX20 in the LNCaP cells promoted cell motility and enhanced the invasive capacity of the LNCaP cells (Fig. 4C–F). Taken together, both loss-of- and gain-of-function experiments demonstrate that DDX20 expression concurrently affects the proliferation, migration and invasiveness of PCa cells.

DDX20 expression correlates with MMP9 levels in PCa tissues

Taking into account the promigratory effect of DDX20 in PCa cell lines and the associated mechanisms reported in other types of cancer, we decided to analyze the expression of MMP9, which has been reported to play a pivotal role in the DDX20-metastasis axis (8), in the same cohorts used in Fig. 1B. Similarly to DDX20, we observed higher mRNA expression levels of MMP9 in the PCa tissues compared with those in the adjacent tissues (Fig. 5A) and there was a positive correlation between DDX20 and MMP9 mRNA levels (Fig. 5B). To further substantiate this finding, we performed immunohistochemical analysis to examine the expression of MMP9 in the same cohort used in Fig. 1C. Notably, similarly to DDX20, the group of PCa patients with high expression of MMP9 were more likely to have a poor prognosis (P=0.036) (Fig. 5D) and similar clinicopathological features were also obtained from the same TMA (Table II) and the same clinicopathological features significantly correlated with MMP9 expression. Taken together, the findings of the present study indicate that DDX20 may also exert effects in PCa through MMP9.

Table II

Correlation between MMP9 expression and key clinicopathological features.

Table II

Correlation between MMP9 expression and key clinicopathological features.

VariableMMP9 (n=99)
LowHighP-value
Age (years)
 ≤5024230.294
 >503220
 Tumor size (cm)
 ≤536200.026a
 >51825
Local infiltration
 Yes11230.002a
 No4223
Gleason grade
 I210.040a
 II–III1634
 IV–V2620

a P<0.05. MMP9, matrix metallopeptidase 9.

DDX20 regulates NF-κB signaling in PCa cell lines

Given the strong correlation between DDX20 and MMP9 in PCa tissues, we then examined whether silencing or ectopically expressing DDX20 would reduce or increase the levels of MMP9, respectively. We found that silencing DDX20 resulted in the inhibition of MMP9 protein levels in the DU145 and PC-3 cell lines (Fig. 6A). Conversely, the ectopic expression of DDX20 resulted in the increased expression of MMP9 in the LNCaP cell line (Fig. 6B). These findings suggest that DDX20 may regulate MMP9 expression in order to enhance the migration and invasiveness of PCa cells. As NF-κB is considered to be the major transcriptional regulator of MMP9 (9,10), we then examined whether the alterations in MMP9 expression following changes in DDX20 levels, are due to NF-κB activity. We performed luciferase reporter assays and the results are shown in Fig. 6C and D; the suppression of DDX20 in the DU145 and PC-3 cells led to the downregulation of NF-κB activity (Fig. 6C). By contrast, the overexpression of DDX20 elevated NF-κB activity (Fig. 6D). Taken together, our findings suggest that DDX20 promotes the migration and invasiveness of PCa cells by regulating the NF-κB-MMP9 axis.

Discussion

In the present study, we report that DDX20 is elevated in the majority of PCa tissue samples and the high expression of DDX20 negatively correlates with patient prognosis. In addition, we have demonstrated that PCa cells with high expression of DDX20 are more prone to be proliferative and invasive.

It has been previously reported that DDX20 increases MMP9 levels which are associated with metastasis and invasion in breast cancer through the activation of NF-κB (8). In the present study, a positive correlation between DDX20 and MMP9 expression was observed in both PCa tissues and cell lines. In addition, the findings of the luciferase reporter assays suggested that DDX20 also exerted promigratory effects through NF-κB signaling in PCa cells. Taken together, these results provide further evidence that DDX20 acts as an oncogenic protein in PCa as well as in breast cancer.

Notably, two other studies have reported that DDX20 acts as a tumor suppressor in HCC. Zender et al employed an oncogenomics-based in vivo RNAi screen that identified DDX20 as a potential tumor suppressor in liver cancer (11). Takata et al revealed that DDX20 suppresses NF-κB activity by regulating miRNA-140 function in order to inhibit the progression of liver cancer (7,12). We are unable to explain the contradictory results observed in studies of DDX20 in different types of cancer. However, given that it exerts disparate effects in various types of cancer through the same pathway, namely the MMP9 and NF-κB signaling pathway, we suggest that the ways in which DDX20 regulates the expression of MMP9 and NF-κB are dependent on the type of cancer. As PCa and breast cancer are gender-related cancers, we suggest that there may be an association between the effects of DDX20 and sex hormones; however, further studies are warranted.

In conclusion, we have demonstrated that there is high expression of DDX20 in PCa tissues and it may be useful as a potential prognostic marker in PCa. In addition, we have examined the biological functions of DDX20 in PCa cell lines. Furthermore, we have provided preliminary evidence for the molecular mechanisms responsible for the effects of DDX20. The contradictory effects of DDX20 in different types of cancer suggest that it may play a key role in the development and progression of cancer and therefore be a potential therapeutic target.

References

1 

Ferlay J, Autier P, Boniol M, Heanue M, Colombet M and Boyle P: Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 18:581–592. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Hankey BF, Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, Ries LA, Merrill RM and Kaplan RS: Cancer surveillance series: interpreting trends in prostate cancer - part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J Natl Cancer Inst. 91:1017–1024. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC and Tucker MA: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 336:1401–1408. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Gallagher RP and Fleshner N: Prostate cancer: 3. Individual risk factors. CMAJ. 159:807–813. 1998.PubMed/NCBI

6 

Beuzeboc P, Soulié M, Richaud P, Salomon L, Staerman F, Peyromaure M, Mongiat-Artus P, Cornud F, Paparel P, Davin JL and Molinié V: Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives. Prog Urol. 19:819–824. 2009.In French. View Article : Google Scholar : PubMed/NCBI

7 

Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, Obi S, Goto T, Kang YJ, Maeda S, Yoshida H, et al: MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression. Hepatology. 57:162–170. 2013. View Article : Google Scholar

8 

Shin EM, Hay HS, Lee MH, Goh JN, Tan TZ, Sen YP, Lim SW, Yousef EM, Ong HT, Thike AA, et al: DEAD-box helicase DP103 defines metastatic potential of human breast cancers. J Clin Invest. 124:3807–3824. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Chou YC, Sheu JR, Chung CL, Chen CY, Lin FL, Hsu MJ, Kuo YH and Hsiao G: Nuclear-targeted inhibition of NF-kappaB on MMP-9 production by N-2-(4-bromophenyl) ethyl caffeamide in human monocytic cells. Chem Biol Interact. 184:403–412. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Ricca A, Biroccio A, Del Bufalo D, Mackay AR, Santoni A and Cippitelli M: bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells. Int J Cancer. 86:188–196. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Zender L, Xue W, Zuber J, Semighini CP, Krasnitz A, Ma B, Zender P, Kubicka S, Luk JM, Schirmacher P, et al: An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell. 135:852–864. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Kudo Y, Goto T, Yoshida H and Koike K: A miRNA machinery component DDX20 controls NF-κB via microRNA-140 function. Biochem Biophys Res Commun. 420:564–569. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June-2016
Volume 37 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chen W, Zhou P and Li X: High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway. Int J Mol Med 37: 1551-1557, 2016
APA
Chen, W., Zhou, P., & Li, X. (2016). High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway. International Journal of Molecular Medicine, 37, 1551-1557. https://doi.org/10.3892/ijmm.2016.2575
MLA
Chen, W., Zhou, P., Li, X."High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway". International Journal of Molecular Medicine 37.6 (2016): 1551-1557.
Chicago
Chen, W., Zhou, P., Li, X."High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway". International Journal of Molecular Medicine 37, no. 6 (2016): 1551-1557. https://doi.org/10.3892/ijmm.2016.2575