Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma

针对白细胞介素-1 受体相关激酶 1 治疗人类肝细胞癌

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作者:Ning Li, Jinhua Jiang, Jing Fu, Ting Yu, Bibo Wang, Wenhao Qin, An Xu, Mengchao Wu, Yao Chen, Hongyang Wang

Background

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.

Conclusion

IRAK1 promotes cell proliferation and protects against apoptosis in HCC, and can be a novel target for HCC treatment.

Methods

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.

Results

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.

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