Circ-MMP2 (circ-0039411) induced by FOXM1 promotes the proliferation and migration of lung adenocarcinoma cells in vitro and in vivo
Autor: | Hongping Huang, Hui Feng, Zhonghua Wei, Xin Lv |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research MMP2 Lung Neoplasms Immunology Adenocarcinoma of Lung Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Transcription (biology) Cell Movement medicine Humans lcsh:QH573-671 Cell Proliferation Messenger RNA Gene knockdown biology Chemistry lcsh:Cytology Cancer stem cells Forkhead Box Protein M1 Cell Biology RNA Circular medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Insulin-like growth factor 2 Cancer research FOXM1 biology.protein Adenocarcinoma Lung cancer |
Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 6, Pp 1-15 (2020) |
ISSN: | 2041-4889 |
Popis: | Numerous reports have stated the significance of cellular events such as proliferation, migration and EMT (epithelial-mesenchymal transition) for cancer development, but the related molecular mechanism remains elusive. FOXM1 (forkhead box transcription M1) is a nuclear co-activator participating in lung adenocarcinoma (LUAD). Thus, this study tried to explain the function of FOXM1 and its downstream molecular mechanism in LUAD. We uncovered FOXM1 upregulation in LUAD and demonstrated that FOXM1 facilitated β-catenin nuclear translocation to activate the transcription of downstream genes. Moreover, we discovered that FOXM1 transcriptionally activated circ0039411 which derived from matrix metallopeptidase 2 (MMP2) (also named as circ-MMP2), while MMP2 is a known downstream target of β-catenin. As for functional investigation, knockdown of circ-0039411 suppressed the proliferation, migration and EMT in LUAD cells and also hindered in vivo growth and metastasis of LUAD tumor. Mechanistically, circ-0039411 enhanced the stability of FOXM1 mRNA by recruiting IGF2BP3 (insulin like growth factor 2 mRNA binding protein 3), thus forming a positive feedback loop. In conclusion, this study revealed that FOXM1-induced circ-MMP2 (circ-0039411) contributes to malignant behaviors of LUAD cells via relying on FOXM1, potentially infusing inspirations for the search of new molecular targets for LUAD treatment. |
Databáze: | OpenAIRE |
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