Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling

Yi,Feng‑Tao; Lu,Qi‑Ping

doi:10.3892/ol.2017.7119

Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling

Authors:
- Feng‑Tao Yi
- Qi‑Ping Lu
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Affiliations: Department of Radiotherapy, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China, Department of General Surgery, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China
Published online on: October 3, 2017 https://doi.org/10.3892/ol.2017.7119
Pages: 7571-7576

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Abstract

Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3). Enforced expression of MUC1 significantly (P<0.05) promoted the clonogenic survival of HCC cells following irradiation compared with empty vector‑transfected cells. MUC1 overexpression resulted in >60% reduction in apoptosis induced by irradiation, as determined by Annexin‑V/propidium iodide double staining and flow cytometry analysis. Furthermore, overexpression of MUC1 significantly (P<0.05) attenuated the activation of caspase‑3 and poly (ADP‑ribose) polymerase in response to irradiation exposure. Mechanistically, MUC1 inhibited irradiation‑induced apoptosis through activation of janus kinase 2 (JAK2) and STAT3, and induction of anti‑apoptotic proteins induced myeloid leukemia cell differentiation protein Mcl‑1 (Mcl‑1) and BCL2 like 1 (Bcl‑xL). Small hairpin RNA‑mediated knockdown of STAT3 or MUC1 resensitized MUC1‑overexpressing cells to irradiation‑induced apoptosis, which was accompanied by reduced expression of Bcl‑xL and Mcl‑1. Collectively, MUC1 contributes to radioresistance of HCC cells likely through activation of the JAK2/STAT3 signaling pathway and thus represents a potential target for improving radiotherapy against HCC.

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