Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma.
Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. However, the role of IRAK1 in hepatocellular carcinoma (HCC) remains little known.



In our study, reverse transcription-PCR (RT-PCR), Western Blot, and immunohistochemical staining were used to assess the mRNA and protein levels of IRAK1 in clinical samples and cell lines. Cell counting assay and flow cytometry were employed to analyze the effect of IRAK1 on cell cycle and apoptosis. Transwell assay was used to study the role of IRAK1 in cell migration. Moreover, subcutaneous xenograft tumor models predict the efficacy of targeting IRAK1 against HCC in vivo.



IRAK1 was over-expressed in HCC tissues and cell lines. Suppression of IRAK1 by small interference RNA (siRNA) or a pharmaceutical IRAK1/4 inhibitor impeded cell growth, induced apoptosis and lessened HCC xenograft tumor growth. Particularly, IRAK1/4 inhibitor treatment caused G1/S cell cycle arrest and apoptosis, confirming IRAK1 as a new therapeutic target for HCC.



IRAK1 promotes cell proliferation and protects against apoptosis in HCC, and can be a novel target for HCC treatment.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Ning
N
Li
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.|The First Clinical Medical College, Fujian Medical University, Fuzhou, 350001, Fujian, China.
Jinhua
J
Jiang
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Jing
J
Fu
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Ting
T
Yu
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Bibo
B
Wang
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Wenhao
W
Qin
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
An
A
Xu
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Mengchao
M
Wu
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China.
Yao
Y
Chen
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. hywangk@vip.sina.com.|International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, 225 Changhai Road, Shanghai, 200438, People's Republic of China. hywangk@vip.sina.com.|National Center for Liver Cancer, Shanghai, 201805, People's Republic of China. hywangk@vip.sina.com.
Hongyang
H
Wang
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation
D034741:RNA, Small Interfering; D053592:Interleukin-1 Receptor-Associated Kinases
Apoptosis; Cell cycle; Hepatocellular carcinoma; IRAK1; Proliferation; Subcutaneous tumor