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Forkhead box protein C1 promotes cell proliferation and invasion in human cervical cancer.

ABSTRACT: Increasing evidence has demonstrated that aberrant forkhead box protein C1 (FOXC1) expression contributes to tumorigenesis in multiple types of malignant tumor. However, the clinical significance and biological roles of FOXC1 in cervical cancer remain unknown. The expression levels of FOXC1 were examined in human cervical cancer tissues and cells using reverse transcription?quantitative polymerase chain reaction, immunohistochemistry and western blotting. Furthermore, high FOXC1 expression was significantly associated with advanced clinical stages, a high degree of malignancy and a poor outcome. FOXC1 silencing inhibited cell growth and enhanced cell apoptosis. Knockdown of FOXC1 markedly suppressed cell migration and invasion in vitro, and resulted in downregulation of phosphorylated?RAC?? serine/threonine?protein kinase, proto?oncogene c?Myc and B?cell lymphoma 2. In conclusion, these data indicated that upregulation of FOXC1 contributed to the development of cervical cancer by increasing the growth and motility of the cervical cancer cells, thereby worsening the disease progression in these patients.

SUBMITTER: Wang L

PROVIDER: S-EPMC5802213 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Forkhead box protein C1 promotes cell proliferation and invasion in human cervical cancer.

Wang Lu L Chai Lulu L Ji Qingchun Q Cheng Rongjie R Wang Jiao J Han Shiyu S

Molecular medicine reports 20180111 3

Increasing evidence has demonstrated that aberrant forkhead box protein C1 (FOXC1) expression contributes to tumorigenesis in multiple types of malignant tumor. However, the clinical significance and biological roles of FOXC1 in cervical cancer remain unknown. The expression levels of FOXC1 were examined in human cervical cancer tissues and cells using reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting. Furthermore, high FOXC1 expression was s ...[more]

PMID: 29328384

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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.

Dataset Information

Forkhead box protein C1 promotes cell proliferation and invasion in human cervical cancer.

Publications

Forkhead box protein C1 promotes cell proliferation and invasion in human cervical cancer.

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