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MiR?122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.

ABSTRACT: MicroRNAs (miRNAs) serve an important role in renal cancer, but renal cancer miRNA expression data remains inconsistent. Therefore, there is a requirement for integrated analysis of these data. An increasing number of studies demonstrate that miR?122 is dysregulated in numerous cancer types, including liver, lung and breast cancer, yet its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, an integrated analysis of four ccRCC miRNAs expression datasets was performed and the expression of miR?122 in the present cohort was validated. The effects of cell proliferation, colony formation, migration and invasion of ccRCC cells in vitro were assayed following transfection with miR?122 mimics and inhibitor. The target gene of miR?122 was confirmed using a luciferase reporter assay, and a xenograft mouse model was used to determine the effect of miR?122 in ccRCC tumorigenicity in vivo. The present results demonstrated that patients with ccRCC with an increased miR?122 level in tumor tissues had a shortened metastasis?free survival time as indicated by The Cancer Genome Atlas?Kidney Renal Clear Cell Carcinoma dataset and the present ccRCC cohort. Overexpression of miR?122 in 786?O cells improved cell proliferation, colony formation, migration and invasion, while knockdown of miR?122 in SN12?PM6 cells inhibited cell growth, colony formation, migration and invasion. Western blot analysis and luciferase reporter assays were used to identify FOXO3 as a direct target of miR?122. The present results indicate that miR?122 serves a tumor?promoting role by direct targeting FOXO3 in ccRCC.

SUBMITTER: Nie W

PROVIDER: S-EPMC6317650 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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miR‑122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.

Nie Wenyuan W Ni Dong D Ma Xin X Zhang Yu Y Gao Yu Y Peng Cheng C Zhang Xu X

International journal of oncology 20181119 2

MicroRNAs (miRNAs) serve an important role in renal cancer, but renal cancer miRNA expression data remains inconsistent. Therefore, there is a requirement for integrated analysis of these data. An increasing number of studies demonstrate that miR‑122 is dysregulated in numerous cancer types, including liver, lung and breast cancer, yet its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, an integrated analysis of four ccRCC miRNAs expression datasets was per ...[more]

PMID: 30483771

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Project description:Background and aim: Understanding the molecular biological mechanisms underlying laryngeal squamous cell carcinoma (LSCC) invasion and metastasis is crucial for diagnosis, treatment, and prognosis. We aimed to examine the expression of the tumor suppressor microRNA-204-5p (miR-204-5p) and its target gene, forkhead box C1 (FOXC1), in human LSCC and explore their roles in the malignant behaviors of LSCC Hep-2 and TU-177 cells. Methods: The regulatory effects of miR-204-5p on the 3' untranslated region of FOXC1 predicted by bioinformatics were tested by dual-luciferase reporter assay. Quantitative RT-PCR was used to detect mRNA expression in 43 fresh samples of LSCC and corresponding adjacent normal mucosa (ANM). FOXC1 protein expression was examined by immunohistochemistry. miR-204-5p mimics and FOXC1 siRNA were transfected into LSCC cell lines Hep-2 and TU-177 to observe malignant behavior. miR-204-5p mimics were injected into Hep-2 or TU-177 xenograft tumors in nude mice to examine tumor growth.Results: The miR-204-5p mRNA level was lower in all 43 LSCC samples than in the ANM samples, but the FOXC1 level was higher in the LSCC samples than in the ANM samples. The miR-204-5p level was lower for stage III and IV cancer and lymph node N+ status samples than for stage I and II cancer and N0 status samples. FOXC1 mRNA and protein levels were higher for N+ than for N0 LSCC. The miR-204-5p mRNA levels were lower in Hep-2 and TU-177 cells than in ANM tissues, but FOXC1 mRNA levels were higher in Hep-2 and TU-177 cells than in ANM tissues. Dual-luciferase reporter assays demonstrated the targeted regulatory effects of miR-204-5p on the FOXC1 3' UTR. Cell proliferation and colony formation was facilitated with miR-204-5p mimics and FOXC1 siRNA, with weaker cell migration and invasion than the controls. Moreover, miR-204-5p overexpression or FOXC1 knockdown inhibited the EMT process in LSCC cells. In vivo experiments demonstrated that injection of miR-204-5p into Hep-2 and TU-177 xenograft tumors in nude mice significantly inhibited tumor growth. Conclusions: miR-204-5p is involved in the invasion and metastasis of LSCC. It has a targeted regulatory effect on FOXC1 expression; malignant LSCC behaviors, including cell proliferation, invasion, and metastasis, are suppressed, and tumor growth in vivo is inhibited. This suggests that miR-204-5p may be a target for molecular therapy of LSCC in the future.

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MiR?122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.

Publications

miR‑122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.

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