MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway, by J.-H. Fu, S. Yang, C.-J. Nan, C.-C. Zhou, D.-Q. Lu, S. Li, H.-Q. Mu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 351-357-DOI: 10.26355/eurrev_201801_14179-PMID: 29424922" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14179.

MiR-130b/TNF-α/NF-κB/VEGFA loop inhibits prostate cancer angiogenesis.

BACKGROUND: Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined. METHODS: We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice. RESULTS: We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer. CONCLUSION: These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.

CD18 inhibits progression of kidney cancer by down-regulating Treg cell levels.

OBJECTIVE: Gene mutation is closely related to the occurrence of tumor. Renal cell carcinoma is a malignant tumor, seriously threatening patients' life quality. Regulatory T cells (Treg) play important roles in the development of several cancers. This study aimed to investigate whether CD18 affects renal carcinoma cell proliferation. MATERIALS AND METHODS: Thirty mice with renal cell carcinoma were constructed using gene-engineering mouse with CD18 deficiency, and another 30 normal C57 mice were used as control. Ki67 and micro-vessel density were detected by using immunohistochemistry (IHC) and immunofluorescence, respectively. The expression of CD3, CD4 and CD8 were detected in blood and spleen by quantitative PCR (q-PCR). Flow cytometry was used to detect the changes of Treg cells. RESULTS: The expression of Ki67 in C57 was significantly higher than that in CD18-/- mice (p<0.05). IHC results showed that CD31 was also significantly downregulated in CD18-/- group compared to control group (p<0.05). It was found that only high expression of CD4 in mesenteric lymph nodes of CD18-/- was considered as non-tumor-bearing. Flow cytometry results showed that Treg cells were significantly decreased in CD18-/- compared to C57 group (p<0.05). CONCLUSIONS: CD18-/- down-regulates Treg cells and inhibits the pathogenesis of renal cell carcinoma.

MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: PI3K/AKT/mTOR signaling pathway plays a crucial role in tumorigenesis and development. It was shown that mTOR overexpression was associated with the pathogenesis of renal cancer. Down-regulation of MiR-182 was found in renal carcinoma tissue. This study thus aims to investigate the influence of miR-182 in regulating mTOR expression and renal carcinoma cell proliferation, invasion, and apoptosis. PATIENTS AND METHODS: The targeted regulatory relationship between miR-182 and mTOR was tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-182 and mTOR expressions. MiR-182, mTOR, p-mTOR, and Survivin levels were compared between HK-2 and A498 cells. Renal carcinoma A498 cells were divided into four groups, including miR-NC, anti-miR-182 mimic, si-NC, and si-mTOR groups. Cell apoptosis and proliferation were evaluated by flow cytometry. Cell invasion was determined by transwell assay. RESULTS: Bioinformatics analysis revealed the complementary relationship between miR-182 and the 3'-UTR of mTOR mRNA. The level of miR-182 was significantly reduced, while mTOR expression was upregulated in renal carcinoma tissue compared with that in benign lesion, which was associated with TNM stage. MiR-182 expression was markedly declined, whereas mTOR, p-mTOR, and Survivin levels were apparently upregulated in A498 cells compared with that in HK-2 cells. The treatment of miR-182 mimic or si-mTOR transfection significantly downregulated mTOR, p-mTOR, and Survivin expressions, restrained cell proliferation and invasion, and enhanced cell apoptosis. CONCLUSIONS: The decreasing level of miR-182 plays a role in enhancing mTOR expression and promoting renal carcinoma pathogenesis. Overexpression of miR-182 inhibited mTOR expression and weakened cell proliferation and invasion, which provides leads to the future therapy of renal cancer.