Effects of MicroRNA-19b on the Proliferation, Apoptosis, and Migration of Wilms' Tumor Cells Via the PTEN/PI3K/AKT Signaling Pathway.

Wilms' tumor (WT) is a most common renal cancer that occurs among children, and microRNA-19b (miR-19b) usually participates in various human cancers. Importantly, the PTEN/PI3K/Akt signaling pathway plays a key role in cell apoptosis, growth and proliferation. Thus, our present study aims to investigate the effect of miR-19b on the PTEN/PI3K/Akt signaling pathway during WT cell proliferation, migration, and apoptosis. WT tissues and adjacent normal tissues from WT patients were collected. qRT-PCR was applied to detect miR-19b expression in both the WT tissues and the adjacent normal tissues, immunohistochemistry was applied to detect the protein expressions of PTEN, P13K, and p-Akt, SK-NEP-1 cells were divided into the blank, negative control (NC), miR-19b mimics and miR-19b inhibitors groups. MTT assay, propidium iodide (PI) staining, Annexin-V/PI double-staining, Transwell assay and Western blotting were performed to examine cell proliferation, cycle, apoptosis, migration, and invasion, and the protein expressions of PTEN, P13K, Akt, and p-Akt. Increased miR-19b expression, positive expression rates of P13K and Akt, decreased PTEN expression rate, a negative correlation between PTEN expression and tumor lymph node metastasis, and a positive correlation between the expression of P13K and Akt and the clinical stages were observed in the WT tissues. The miR-19b inhibitors group exhibited decreased cell proliferation, cell cycle progression, migration and invasion, and protein expressions of PI3K and p-Akt but increased PTEN protein expression compared with the blank and NC groups. Thus, inhibition of miR-19b suppresses the progression of WT by modulating the PTEN/PI3K/AKT signaling pathway. J. Cell. Biochem. 118: 3424-3434, 2017. © 2017 Wiley Periodicals, Inc.

Liu GL ，Yang HJ ，Liu B ，Liu T ... -  《-》

MiR-155-5p exerts tumor-suppressing functions in Wilms tumor by targeting IGF2 via the PI3K signaling pathway.

MicroRNA-155-5p (miR-155-5p) has been reported to play an oncogenic role in different human malignancies; however, its role in Wilms tumor (WT) remains unclear. Differentially expressed miRNAs (DE-miRNAs) and mRNAs (DEGs) in WT blood and tissues were identified by using miRNA microarray and RNA-sequencing. Bioinformatics prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the potential functions of DE-miRNAs. DE-miRNAs and DEGs in WT obtained from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were identified by using the "edgeR" package. RT-qPCR was used to explore miR-155-5p and IGF2 expression and their clinical significance in WT specimens. A rhabdoid cell line (G401) and Ewing sarcoma cell line (SK-NEP-1) were used. Immunohistochemical staining, western blotting and dual-luciferase reporter assays were performed to study the mechanisms involved. The CCK-8, flow cytometry, wound healing and transwell assays were performed to identify the effects of miR-155-5p and IGF2 knockdown on cell proliferation, apoptosis, migration and invasion, respectively. MiR-155-5p was downregulated in both blood and tissues from WT patients who did not receive chemotherapy before surgery but was upregulated in tissues from WT patients who had received chemotherapy before surgery. IGF2, PI3K, AKT and mTOR were found to be upregulated in WT tissues. Additionally, miR-155-5p and IGF2 were significantly correlated with TNM stage and lymphatic metastasis in WT patients. Molecular mechanism exploration indicated that IGF2 was downregulated by miR-155-5p via direct binding to its 3' untranslated region in cell lines. Furthermore, IGF2, PI3K, AKT and mTOR expression was inversely correlated with miR-155-5p expression, and PI3K, AKT and mTOR expression was positively correlated with IGF2 expression in cell culture. Functional studies demonstrated that miR-155-5p upregulation and IGF2 knockdown suppressed cell proliferation, migration and invasion and induced cell apoptosis. Moreover, the tumor-suppressing effects of miR-155-5p in cells were abrogated by miR-155-5p inhibitor treatment. Taken together, these findings suggest that miR-155-5p functions as a tumor suppressor in WT through inactivating the PI3K/AKT/mTOR signaling pathway by directly targeting IGF2. Thus, miR-155-5p might be a novel therapeutic target for WT.

Luo X ，Dong J ，He X ，Shen L ，Long C ，Liu F ，Liu X ，Lin T ，He D ，Wei G ... -  《-》

MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer.

Wu YR ，Qi HJ ，Deng DF ，Luo YY ，Yang SL ... -  《-》

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

Cui M ，Liu W ，Zhang L ，Guo F ，Liu Y ，Chen F ，Liu T ，Ma R ，Wu R ... -  《-》

Up-regulation of miR-190b promoted growth, invasion, migration and inhibited apoptosis of Wilms' tumor cells by repressing the PTEN expression.

An NN ，Shawn J ，Peng JP ，Wu MD ，Huang LG ... -  《-》