Circ-MMP2 (circ-0039411) induced by FOXM1 promotes the proliferation and migration of lung adenocarcinoma cells in vitro and in vivo.

Cell Death & Disease
Xin LvZhonghua Wei

Abstract

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...Continue Reading

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Citations

Nov 6, 2021·The International Journal of Biological Markers·Xiaohui WenXun Wang

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Methods Mentioned

BETA
transfection
xenografts
nuclear translocation
electrophoresis
PCR
ChIP
RIP
pull down
dissection
fluorescence microscopy

Software Mentioned

Graphpad Prism

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