Validation of Bmi1 as a therapeutic target of hepatocellular carcinoma in mice.
Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However, whether Bmi1 can be used as a potential target for hepatocellular carcinoma treatment has not been fully confirmed yet. Here, we show that perturbation of Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and tumor growth of hepatocellular carcinoma cells both in vitro and in vivo. Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating stages and the fast growing stages. Cellular biology analysis revealed that Bmi1 knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents.
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. qi601960314@gmail.com.
Shibo
S
Qi
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tjlibin@hust.edu.cn.
Bin
B
Li
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. M201475282@hust.edu.cn.
Tan
T
Yang
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. liuxiulankl@gmail.com.
Yong
Y
Liu
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. M201475285@hust.edu.cn.
Shanshan
S
Cao
Department of Hepatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xxhe@tjh.tjmu.edu.cn.
Xingxing
X
He
Department of Oncology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. pengzhang@tjh.tjmu.edu.cn.
Peng
P
Zhang
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. M201475065@hust.edu.cn.
Lei
L
Li
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xcr@hust.edu.cn.
Chuanrui
C
Xu
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D000903:Antibiotics, Antineoplastic; C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004317:Doxorubicin; D063150:Polycomb Repressive Complex 1