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MicroRNA-183 promotes the proliferation and metastasis of renal cell carcinoma through targeting Dickkopf-related protein 3.

ABSTRACT: Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy and radiotherapy, and its prognosis remains poor. Targeted therapy is a novel technique for the treatment of RCC. The present study aimed to determine the precise effects of microRNA-183 (miR-183) on RCC. Reverse transcription-quantitative polymerase chain reaction analysis was conducted in order to analyze the expression level of miR-183 in RCC cell lines. Cell transfection, viability assays and invasion assays were also performed, followed by western blot analysis and a luciferase reporter assay, in order to examine the effects of miR-183. The expression of miR-183 was upregulated in all four RCC cell lines compared with the immortalized normal proximal tubule epithelial HK-2 cell line. The cell viability and invasion assays demonstrated that decreased expression of miR-183 suppressed RCC cell proliferation and invasion in vitro. Furthermore, the present study identified that Dickkopf-related protein-3 (DKK-3) was a direct target of miR-183 in RCC. The results demonstrated that miR-183 functioned as an oncogene by downregulating DKK-3 expression and that it provided a potential diagnostic, prognostic and therapeutic target for RCC.

SUBMITTER: Zhang XL

PROVIDER: S-EPMC5840664 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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MicroRNA-183 promotes the proliferation and metastasis of renal cell carcinoma through targeting Dickkopf-related protein 3.

Zhang Xiao-Long XL Xu Gang G Zhou Yi Y Yan Jia-Jun JJ

Oncology letters 20180208 4

Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy and radiotherapy, and its prognosis remains poor. Targeted therapy is a novel technique for the treatment of RCC. The present study aimed to determine the precise effects of microRNA-183 (miR-183) on RCC. Reverse transcription-quantitative polymerase chain reaction analysis was conducted in order to analyze the expression level of miR-183 in RCC cell lines. Cell transfection, viability assays and invasion assays were also per ...[more]

PMID: 29552228

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Project description:BackgroundBreast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer.MethodsqRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan-Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial-mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo.ResultsPlasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo.ConclusionsThese results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21-LZTFL1-EMT axis might be a promising strategy in breast cancer therapy.Trial registrationRetrospectively registered.

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MicroRNA-183 promotes the proliferation and metastasis of renal cell carcinoma through targeting Dickkopf-related protein 3.

Publications

MicroRNA-183 promotes the proliferation and metastasis of renal cell carcinoma through targeting Dickkopf-related protein 3.

Similar Datasets

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