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The Rad51\u2010related protein XRCC<\/jats:styled-content>3 plays roles in the recombinational repair of DNA<\/jats:styled-content> double\u2010strand breaks to maintain chromosome stability and repair DNA<\/jats:styled-content> damage. The present study aimed to investigate the effect of XRCC<\/jats:styled-content>3 on the radiotherapy response of ESCC<\/jats:styled-content> and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC<\/jats:styled-content>3 expression in ESCC<\/jats:styled-content> cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC<\/jats:styled-content>3 expression was positively correlated with resistance to chemoradiotherapy in ESCC<\/jats:styled-content> and an independent predictor for short disease\u2010specific survival of ESCC<\/jats:styled-content> patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro<\/jats:italic> and in vivo<\/jats:italic> was substantially increased by knockdown of XRCC<\/jats:styled-content>3 in ESCC<\/jats:styled-content> cells. Ectopic overexpression of XRCC<\/jats:styled-content>3 in both XRCC<\/jats:styled-content>3\u2010silenced ESCC<\/jats:styled-content> cells dramatically enhanced ESCC<\/jats:styled-content> cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC<\/jats:styled-content>3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC<\/jats:styled-content> cell death by radiation\u2010induced apoptosis and mitotic catastrophe. Our data suggest that XRCC<\/jats:styled-content>3 protects ESCC<\/jats:styled-content> cells from ionizing radiation\u2010induced death by promoting DNA<\/jats:styled-content> damage repair and\/or enhancing telomere stability. XRCC<\/jats:styled-content>3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12820","type":"journal-article","created":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T16:05:18Z","timestamp":1442592318000},"page":"1678-1686","source":"Crossref","is-referenced-by-count":21,"title":["XRCC<\/scp>3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma"],"prefix":"10.1111","volume":"106","author":[{"given":"Jingjing","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Radiotherapy Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiran","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Key Laboratory of Cancer 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