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) contributes to malignant behaviors of LUAD cells via relying on FOXM1, potentially infusing inspirations for the search of new molecular targets for LUAD treatment.
Highlights
Lung cancer belongs to a kind of primary cause of cancer-induced deaths in the world
Silencing FOXM1 abrogated cell proliferation, migration, and EMT in lung adenocarcinoma (LUAD) cells and restrained LUAD tumor growth and metastasis in vivo First, we tried to comprehend the role of FOXM1 in LUAD
Afterwards, quantitative real-time polymerase chain reaction (qRT-PCR) confirmed the higher expression of FOXM1 in LUAD cells (A549, HCC827, PC-9, NCIH1975 and NCI-H1299) than that in normal 16HBE cells (Fig. 1b), and two cell lines (A549 and HCC827) expressing the highest FOXM1 level were chosen for later use
Summary
Lung cancer belongs to a kind of primary cause of cancer-induced deaths in the world. There was at least 1.6 million patients confirmed as lung cancer and not less than 1.5 million people died from lung cancer around the world in 20121. Lung adenocarcinoma (LUAD) is a common subtype of lung cancer[2]. Even though there are many improvements in the treatment of LUAD, the 5year survival rate of LUAD patient is still poor[3]. Patients with LUAD usually lack obvious clinical symptoms, which seriously delays the diagnosis and treatment of LUAD and leads to dim chance for them to receive useful LUAD treatment.
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