Lamin B2 binding to minichromosome maintenance complex component 7 promotes non-small cell lung carcinogenesis

// Yinan Ma 1 , Liangru Fei 1 , Meiyu Zhang 1 , Wenzhu Zhang 1 , Xiaofang Liu 2 , Congcong Wang 2 , Yuan Luo 1 , Haiyan Zhang 4 and Yuchen Han 1, 2, 3 1 Departments of Pathology, School of Basic Medical Sciences, China Medical University, Liaoning, China 2 Department of Pathology, The First Affiliated Hospital of China Medical University, Liaoning, China 3 Department of Pathology, Shanghai Chest Hospital, Shanghai, China 4 Department of Pathology, The First People’s Hospital of Jining, Shandong, China Correspondence to: Yuchen Han, email: ychan@cmu.edu.cn Keywords: lamin B2; MCM7; DNA replication; NSCLC Abbreviations: NSCLC: non-small cell lung cancer; MCM7: Minichromosome maintenance complex component 7 Received: January 04, 2017      Accepted: July 17, 2017      Published: August 18, 2017 ABSTRACT We investigated the role of lamin B2 in non-small cell lung cancer (NSCLC). We detected higher lamin B2 expression in 20 NSCLC tumor tissues obtained from The Cancer Genome Atlas than in adjacent normal lung tissues. LMNB2-RNAi knockdown in A549 and H1299 NSCLC cells inhibited colony formation, cell proliferation and G1-S cell cycle progression while increasing apoptosis. LMNB2 overexpression had the opposite effects. Tumor xenograft experiments showed diminished tumor growth with LMNB2 knockdown H1299 cells than with controls. Yeast two-hybrid studies revealed minichromosome maintenance complex component 7 (MCM7) to be a binding partner of lamin B2, which was confirmed by co-immunoprecipitation and co-localization studies. Lamin B2 binding enhanced DNA binding and helicase activities of MCM7. Deletion analysis with MCM7-N, MCM7-M or MCM7-C mutant proteins showed that lamin B2 binds to the C-terminus of MCM7, and competes with the binding of the tumor suppressor retinoblastoma (RB) protein. Immunohistochemical analysis of 150 NSCLC patient samples revealed that both lamin B2 and MCM7 levels positively correlated with histological grade and tumor TNM stage. Moreover, high lamin B2 and MCM7 levels correlated with shorter overall survival of NSCLC patients. In sum, these results show that lamin B2 interaction with MCM7 promotes NSCLC progression.