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This clinical characteristic reduces the efficacy of chemotherapeutic agents in the treatment of recurrence or metastasis following surgical resection. Understanding the mechanism of chemotherapy resistance in renal cell carcinoma remains a significant challenge. In this study, we have shown that varied level of XPF expression was organ\u2010tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively. The expression of XPF was significantly higher in renal cancer than in bladder cancer and testicular cancer and correlated with the clinical characteristic of their chemotherapeutics sensitivity. These novel findings proposed that the intrinsic chemoresistance of human renal cell carcinomas might be derived from the high level of XPF expression. In a panel of five cancer cell lines, decreasing cisplatin sensitivity correlated with increasing levels of XPF expression. Knockdown of XPF expression not only increased sensitivity of renal carcinoma cells to cisplatin treatment by affecting the DNA damage response, including DNA repair, cell cycle regulation and apoptosis, but also increased senescence of renal cancer cell. Furthermore, experiment <jats:italic>in vivo<\/jats:italic> confirmed that silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor. These findings firstly uncover a partial mechanism of intrinsic chemoresistance in renal cancer and may provide a new approach to break through the obstacle of intrinsic chemoresistance by targeting the XPF protein with a potential new inhibitor.<\/jats:p>","DOI":"10.1002\/ijc.30396","type":"journal-article","created":{"date-parts":[[2016,8,20]],"date-time":"2016-08-20T09:02:52Z","timestamp":1471683772000},"page":"2827-2837","source":"Crossref","is-referenced-by-count":19,"title":["Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma"],"prefix":"10.1002","volume":"139","author":[{"given":"Qiao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Urology Chongqing Oncology Hospital Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Fu","sequence":"additional","affiliation":[{"name":"Urology Institute of PLA, Southwest Hospital, The Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Pan","sequence":"additional","affiliation":[{"name":"Urology Institute of PLA, Southwest Hospital, The Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Urology Institute of PLA, Southwest Hospital, The Third Military Medical University, Chongqing, China"},{"name":"Southwest Cancer Center, Southwest Hospital, The Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60229-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.06.048"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.06.017"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2442"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e32835fc857"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/CAD.0b013e3283609ec1","article-title":"Chemotherapy in metastatic renal cell carcinoma today? 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