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Dicer suppresses MMP-2-mediated invasion and VEGFA-induced angiogenesis and serves as a promising prognostic biomarker in human clear cell renal cell carcinoma
- Source :
- Oncotarget
- Publication Year :
- 2016
-
Abstract
- // Yan-Su Chen 1, 2, * , Fei Meng 1, 3, * , Hai-Long Li 1, * , Qing-Hua Liu 1, 4 , Ping-Fu Hou 1, 5 , Jin Bai 1, 5 , Jun-Nian Zheng 1, 5 1 Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China 2 School of Public Health, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China 3 Department of Obstetrics and Gynecology, Huai’ an First People's Hospital, Nanjing Medical University, Huai’ an 223300, Jiangsu Province, China 4 Department of Pathology, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China 5 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China * These authors contributed equally to this work Correspondence to: Jin Bai, email: bj@xzhmu.edu.cn Jun-Nian Zheng, email: jnzheng@xzhmu.edu.cn Keywords: dicer, metastasis, angiogenesis, prognostic biomarker, renal cell carcinoma Received: May 16, 2016 Accepted: October 02, 2016 Published: October 08, 2016 ABSTRACT Dicer, a key component of the microRNA processing machinery, has been reported to exert discrepant prognostic values and biological roles in different types of cancers. Here, we investigated the function and prognostic value of Dicer in clear cell renal cell carcinoma (ccRCC). Using the retrospective ccRCC patients’ cohorts with tissue microarray (TMA), we demonstrated that Dicer expression was significantly down-regulated in ccRCC compared with renal non-tumor tissues, and negatively associated with pN status ( P = 0.005), pM status ( P = 0.009) and TNM stage ( P =0.013). Multivariate Cox proportional hazards regression analyses showed that positive Dicer expression was an independent favorable factor for prognosis of ccRCC patients (hazard ratio (HR) = 0.709, P = 0.025 for 5-year overall survival; HR = 0.655, P = 0.008 for disease specific survival). Moreover, we found that Dicer decreased the abilities of cell migration, invasion and angiogenesis through suppressing MMP-2 and VEGFA expression. Tumor metastasis model in vivo showed much more metastatic nodules of lung in the Dicer knockdown group than the control group via increased MMP-2 expression. Our findings imply that Dicer inhibits ccRCC metastasis and may serve as promising prognostic biomarkers for ccRCC patients.
- Subjects :
- 0301 basic medicine
Oncology
Ribonuclease III
Vascular Endothelial Growth Factor A
Pathology
Angiogenesis
Kaplan-Meier Estimate
Metastasis
DEAD-box RNA Helicases
angiogenesis
0302 clinical medicine
Renal cell carcinoma
Medicine
prognostic biomarker
Cells, Cultured
Mice, Inbred BALB C
Tissue microarray
biology
Neovascularization, Pathologic
Prognosis
Kidney Neoplasms
Vascular endothelial growth factor A
030220 oncology & carcinogenesis
Matrix Metalloproteinase 2
Female
RNA Interference
Research Paper
medicine.medical_specialty
renal cell carcinoma
Mice, Nude
03 medical and health sciences
Internal medicine
Cell Line, Tumor
Biomarkers, Tumor
Animals
Humans
metastasis
Neoplasm Invasiveness
Carcinoma, Renal Cell
Retrospective Studies
dicer
business.industry
Cancer
medicine.disease
Xenograft Model Antitumor Assays
Clear cell renal cell carcinoma
030104 developmental biology
RNAi Therapeutics
biology.protein
business
Dicer
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 51
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....ce23edeaf4044cffdc164809290f4472