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MCM4 acts as a biomarker for LUAD prognosis
Authors:Yue Tan  Lei Ding  Guiyuan Li
Institution:1. Branch of Minhang, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

Contribution: Conceptualization (equal), ​Investigation (equal);2. Department of Ultrasonic Diagnosis, Second Affiliated Hospital of Anhui Medical University, Hefei, China

Contribution: Conceptualization (equal), ​Investigation (equal);3. Department of Oncology, School of Medicine, Tongji Hospital, Tongji University, Shanghai, China

Abstract:MCM4 forms the pre-replication complex (MCM2-7) with five other minichromosome maintenance (MCM) proteins. This complex binds to replication origins at G1 stage in cell cycle process, playing a critical role in DNA replication initiation. Recently, MCM4 is reported to have a complex interaction with multiple cancer progression, including gastric, ovarian and cervical cancer. Here, this study mainly focused on the expression of MCM4 and its values in lung adenocarcinoma (LUAD). MCM4 was highly expressed in LUAD tumours and cells, and had an important effect on the overall survival. Overexpression of MCM4 promoted the proliferation, and suppressed the apoptosis in LUAD cells. However, MCM4 silence led to the opposite results. In vivo, knockdown of MCM4 inhibited tumour volume and weight in xenograft mouse model. As a member of DNA helicase, knockdown of MCM4 caused cell cycle arrest at G1 stage through inducing the expression of P21, a CDK inhibitor. These findings indicate that MCM4 may be a possible new therapeutic target for LUAD in the future.
Keywords:cell cycle  lung adenocarcinoma  MCM4  overall survival  P21
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