Academic Journal
FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression
| العنوان: | FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression |
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| المؤلفون: | Guohui Hu, Zhengwei Yan, Cheng Zhang, Minzhang Cheng, Yehong Yan, Yiting Wang, Libin Deng, Quqin Lu, Shiwen Luo |
| المصدر: | Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-17 (2019) |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | FOXM1, KIF4A, Hepatocellular carcinoma, Proliferation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Background Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor of the forkhead box proteins superfamily, which includes four isoforms FOXM1a, b, c, and d. FOXM1 has been implicated in hepatocellular carcinoma (HCC) progression, but the underlying molecular mechanism remains elusive. In this study, we aim to clarify the molecular basis for FOXM1-mediated HCC progression. Methods Bioinformatic analysis was used to explore the differentially expressed genes predicting HCC proliferation. The expression of FOXM1 and kinesin family member (KIF)4A was confirmed by western blotting and immunohistochemistry in HCC tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of FOXM1 and KIF4A on HCC. The effect of FOXM1 on the regulation of KIF4A expression was studied in cell biology experiments. The interaction between KIF4A and FOXM1 was analyzed by chromatin immunoprecipitation and luciferase experiments. A series of experiments was performed to explore the functions of FOXM1/KIF4A in HCC progression, such as cell proliferation, cell growth, cell viability, and cell cycle. A xenograft mouse model was used to explore the regulatory effect of FOXM1-KIF4A axis on HCC tumor growth. Results FOXM1 and KIF4A were overexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and are significant risk factors for HCC recurrence and shorter survival. We found that KIF4A was dominantly regulated by FOXM1c among the four isoforms, and further identified KIF4A as a direct downstream target of FOXM1c. Inhibiting FOXM1 decreased KIF4A expression in HCC cells, whereas its overexpression had the opposite effect. FOXM1-induced HCC cell proliferation was dependent on elevated KIF4A expression as KIF4A knockdown abolished FOXM1-induced proliferation of HCC cells both in vitro and in vivo. Conclusion The FOXM1–KIF4A axis mediates human HCC progression and is a potential therapeutic target for HCC treatment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1756-9966 43402488 |
| Relation: | http://link.springer.com/article/10.1186/s13046-019-1202-3; https://doaj.org/toc/1756-9966 |
| DOI: | 10.1186/s13046-019-1202-3 |
| URL الوصول: | https://doaj.org/article/e9ccc4a43402488495c30ad5676ad6dc |
| رقم الانضمام: | edsdoj.9ccc4a43402488495c30ad5676ad6dc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17569966 43402488 |
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| DOI: | 10.1186/s13046-019-1202-3 |