Abstract
BackgroundInterleukin-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.MethodsIn 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.ResultsIRAK1 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.ConclusionIRAK1 promotes cell proliferation and protects against apoptosis in HCC, and can be a novel target for HCC treatment.
Highlights
Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies
IRAK1 was over-expressed in hepatocellular carcinoma (HCC) tumor tissues The mRNA and protein level of IRAK1 was investigated in 33 clinical HCC specimens
We found that IRAK1 was highly expressed in the HCC tissues comparing with adjacent normal tissues by immunohistochemical staining (Fig. 1a)
Summary
Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. Li et al Journal of Experimental & Clinical Cancer Research (2016) 35:140 process and results in the activation of IRAK1. In this process, the threonine 209 (T209) is vital for IRAK1 kinase activity [13,14,15]. In some malignant tumors, disordered inflammatory toll-like receptor (TLR) signaling is related to up-regulated NF-kB activity. The IRAK family members are mediators of TLR/IL1R signal pathways, and amounts of evidence implicate that these kinases including IRAK1 are vital cancer targets [19, 20]. The roles of IRAK1 in HCC have not been investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
