机构:[1]Shenzhen Hospital, Southern Medical University, Shenzhen, China南方医科大学深圳医院深圳医学信息中心[2]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China[3]Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China[4]Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China[5]Zhujiang Hospital, Southern Medical University, Guangzhou, China[6]Zhongshan Huangpu People's Hospital, Zhongshan, Guangdong, China[7]The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
RNA polymerase I subunit D (POLR1D), which is involved in synthesis of ribosomal RNA precursors and small RNAs, has been shown to be overexpressed in several human cancer types. Nevertheless, the role of POLR1D in the progression of colorectal cancer (CRC) remains unknown. The following study aimed to investigate the role and underlying mechanism of POLR1D in CRC progression. In this report, we found that POLR1D was significantly up-regulated in CRC through data mining of oncomine database. Furthermore, the immunohistochemistry (IHC) staining of a tissue microarray (TMA) of 75 human CRC patients showed that the expression level of POLR1D was positively correlated to tumor size and poor survival of CRC patients. Aberrant expression of POLR1D significantly promoted cell proliferation and migration in vitro, as well as tumor growth in vivo. Conversely, POLR1D knockdown displayed the opposite effects. The flow Cytometry assays showed that POLR1D fostered cell cycle progression at G1-S transition and inhibited cell apoptosis. Finally, at the molecular level, we demonstrated that POLR1D-induced the promotion of G1-S cell cycle transition was mediated by activation of wnt-β-catenin signaling and inactivation of p53 signaling. Our results suggested that POLR1D may function as a risk factor for predicting the outcome of CRC patients, as well as a potential therapeutic target for CRC.
基金:
National Natural Science Foundation of China,Grant numbers: 81573729, 81603472,81673890
第一作者机构:[1]Shenzhen Hospital, Southern Medical University, Shenzhen, China[2]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
共同第一作者:
通讯作者:
通讯机构:[1]Shenzhen Hospital, Southern Medical University, Shenzhen, China[2]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China[5]Zhujiang Hospital, Southern Medical University, Guangzhou, China[7]The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China[*1]The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.[*2]Shenzhen Hospital, Southern Medical University, Shenzhen, China[*3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
推荐引用方式(GB/T 7714):
Mingqing Wang,Wenbo Niu,Rong Hu,et al.POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients.[J].MOLECULAR CARCINOGENESIS.2019,58(5):735-748.doi:10.1002/mc.22966.
APA:
Mingqing Wang,Wenbo Niu,Rong Hu,Yanjing Wang,Yangyang Liu...&Wei Xiao.(2019).POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients..MOLECULAR CARCINOGENESIS,58,(5)
MLA:
Mingqing Wang,et al."POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients.".MOLECULAR CARCINOGENESIS 58..5(2019):735-748