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MiR-210-3p inhibits the tumor growth and metastasis of bladder cancer via targeting fibroblast growth factor receptor-like 1.

ABSTRACT: Current evidence indicates that microRNAs are widely down-regulated in various tumors including colorectal carcinoma, liver cancer and lung cancer, and function as tumor suppressors through inhibiting cancer cell growth, invasion and migration. Here, we demonstrated that miR-210-3p level was significantly reduced in the bladder cancer compared to paratumor tissues, and attempt to reveal the regulatory role of miR-210-3p in bladder cancer progression. Exogenous overexpression of miR-210-3p inhibited the proliferation, migration and invasion of bladder cancer cells in vitro. In addition, the nude mouse xenograft model showed that miR-210-3p over-expressing inhibited bladder cancer growth and liver metastasis whereas silencing miR-210-3p caused an opposite outcome, which is mainly regulated by targeting fibroblast growth factor receptor-like 1 (FGFRL1). We also demonstrated that the expression of FGFRL1 in bladder cancer specimens were negatively correlated with miR-210-3p level, and FGFRL1 overexpression rescued the cell proliferation and invasion inhibited by ectopic expression of miR-210-3p. Moreover, knockdown of FGFRL1 was able to mimic the cell growth and metastasis effects induced by miR-210-3p over-expressing in bladder cancer cells. Together, these results indicate that miR-210-3p plays an important role in the regulation of bladder cancer growth and metastasis in vitro and in vivo through targeting FGFRL1.

SUBMITTER: Yang X

PROVIDER: S-EPMC5574945 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective:Mounting research has established the role of microRNAs (miRNAs) as oncogenes or anti-oncogenes (tumor suppressors) in the development and progression of several cancers. The purpose of our current study is to delineate the roles and functional mechanisms of miR-331-3p and MLLT10 in non-small cell lung cancer (NSCLC) tumorigenesis. Patients and Methods:Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was employed to measure miR-331-3p expression levels in twenty-six matched tumor tissues and non-cancerous tissues collected from patients suffering from NSCLC, and from six NSCLC cell lines separately: A549, H1650, H292, H1299, H1944 and BEAS-2b. We employed the dual-luciferase activity assay to check whether the putative gene, MLLT10, was a downstream target of miR-331-3p in NSCLC pathogenesis and development. Western blot was conducted to analyze the protein expression levels of MLLT10 (AF10), E-cadherin, Vimentin, and GAPDH. CCK-8 assay, transwell migration assay, and transwell invasion assay were carried out to observe the functions of miR-331-3p and MLLT10 on NSCLC tumor cell proliferation, metastasis, and invasion, respectively. To identify whether the metastasis of NSCLC tumor cells was EMT-mediated, supplementary experiments involving E-cadherin and Vimentin were implemented. Results:miR-331-3p was downregulated in NSCLC, which promoted tumor cell proliferation, whereas the overexpression of miR-331-3p inhibited tumor cell proliferation. Being a direct target of miR-331-3p, MLLT10 was negatively modulated by miR-331-3p, which suppressed tumor cell proliferation, migration, and invasion in NSCLC. However, MLLT10 overexpression alleviated the above inhibitory effects. Furthermore, EMT-mediated metastasis was proved to be present in NSCLC. Conclusion:miR-331-3p played a suppressor role in NSCLC tumor cell proliferation, EMT-mediated metastasis, and invasion by targeting MLLT10. Our findings highlighted that miR-331-3p/MLLT10 axis could be useful as a clinical diagnostic marker and therapeutic target in NSCLC patients.

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MiR-210-3p inhibits the tumor growth and metastasis of bladder cancer via targeting fibroblast growth factor receptor-like 1.

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