Tohoku J. Exp. Med., 2017 May, 242(1)

Over-Expression of miR-21 and Lower PTEN Levels in Wilms' Tumor with Aggressive Behavior

MINGYU CUI,¹ WEI LIU,¹ LIJUAN ZHANG,¹ FENG GUO,¹ YANG LIU,¹ FANG CHEN,² TING LIU,³ RUI MA⁴ and RONGDE WU¹

¹Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong University,Jinan, Shandong Province, China
²Shandong Quality Inspection Center for Medical Devices, Jinan, Shandong Province, China
³Qilu Children's Hospital of Shandong University, Jinan, Shandong Province, China
⁴Shandong Medical Imaging Research Institute, Jinan, Shandong Province, China

Wilms' tumor (WT) is the most common pediatric kidney tumor. MiR-21 is one of the most frequently overexpressed microRNAs in solid tumors, while phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is the most highly mutated tumor suppressor gene. The aim of this study was to investigate the relationship between miR-21 and PTEN in WT. The expression levels of miR-21 and the PTEN protein were determined by qRT-PCR and Western blot analyses in WT specimens, respectively. In WT tissues, the miR-21 expression levels were significantly higher and the PTEN protein levels were significantly lower, compared to the adjacent non-tumorous renal tissues. The higher levels of miR-21 and lower levels of PTEN were correlated with age (> 24 months), late clinical stage, unfavorable histopathological type and lymphatic metastasis. A univariate linear regression analysis indicated a significant correlation between higher miR-21 levels and lower PTEN levels. Using the SK-NEP-1 WT cell line, we showed that the decreased expression levels of miR-21 promoted cell proliferation and invasion, but inhibited apoptosis. Importantly, lowered expression levels of miR-21 increased the expression levels of PTEN protein and decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT), each of which functions in the downstream signaling pathway. Dual luciferase-reporter assays indicated that PTEN mRNA was a direct target of miR-21. In conclusion, higher miR-21 levels and lower PTEN protein levels are predictive biomarkers for poor prognosis of WT patients. Over-expression of miR-21 promotes aggressive behavior of WT by targeting PTEN.

keywords —— miR-21; PTEN; SK-NEP-1 cell; target gene; Wilms' tumor

© 2017 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2017, 242, 43-52

Correspondence: Rui Ma, Shandong Medical Imaging Research Institute, 324 Jingwu Road, Jinan, Shandong Province 250021, China.

e-mail: mary.03@163.com

Correspondence: Rongde Wu, Department of pediatric surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong Province 250021, China.

e-mail: sdu-submit@hotmail.com