Abstract
DNA replication control is vital for maintaining genome stability and the cell cycle, perhaps most notably during cell division. Malignancies often exhibit defective minichromosome maintenance protein 2 (MCM2), a cancer proliferation biomarker that serves as a licensing factor in the initiation of DNA replication. MCM2 is also known to be one of the ATPase active sites that facilitates conformational changes and drives DNA unwinding at the origin of DNA replication. However, the biological networks of MCM2 in lung cancer cells via protein phosphorylation remain unmapped. The RNA-seq datasets from The Cancer Genome Atlas (TCGA) revealed that MCM2 overexpression is correlated with poor survival rate in lung cancer patients. To uncover MCM2-regulated functional networks in lung cancer, we performed multi-dimensional proteomic approach by integrating analysis of the phosphoproteome and proteome, and identified a total of 2361 phosphorylation sites on 753 phosphoproteins, and 4672 proteins. We found that the deregulation of MCM2 is involved in lung cancer cell proliferation, the cell cycle, and migration. Furthermore, HMGA1S99 phosphorylation was found to be differentially expressed under MCM2 perturbation in opposite directions, and plays an important role in regulating lung cancer cell proliferation. This study therefore enhances our capacity to therapeutically target cancer-specific phosphoproteins.
Highlights
Lung cancer is the leading cause of cancer-related mortality accounting for about 27% of all cancer deaths per year[1]
Recent studies have profiled the protein expression of the DNA replication licensing factor, minichromosome maintenance protein 2–7 complex (MCM2–7), which is correlated with cancer progression[10]
Overexpression of MCM2 correlates with poor survival rate in lung cancer patients
Summary
Lung cancer is the leading cause of cancer-related mortality accounting for about 27% of all cancer deaths per year[1]. The deregulation of protein interactions in DNA replication, proliferation, and the cell cycle are some of the key factors involved in cancer development and progression[4,5]. Despite efforts to comprehend how phosphorylation regulates initiation of DNA synthesis[15,16], the biological networks of MCM2-7 in lung cancer cells via protein phosphorylation remain unmapped. We perform large-scale analysis of the phosphoproteome and proteome to characterize and interpret MCM2, in an attempt to establish a global functional distribution of the identified phosphoproteins and phosphosites in both overexpressed and silenced MCM2 lung cancer cells. Our results provide a comprehensive insight into the regulatory role of MCM2 in lung cancer, and reveal that MCM2 promotes cell proliferation might possibly via the regulation of high mobility group protein HMG-I/HMG-Y (HMGA1) phosphorylation. Understanding the molecular interactions of MCM2 in lung cancer cells enhances our capacity to therapeutically target cancer-specific phosphoproteins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
