CircPOFUT1 fosters colorectal cancer metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1
Fei Long,
Buning Tian,
Liang Li,
Min Ma,
Zhijian Chen,
Guojiang Tan,
Ning Yin,
Chonglei Zhong,
Bowen Yu,
Yihang Guo,
Miao Chen,
Gui Hu
Affiliations
Fei Long
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Postdoctoral Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Buning Tian
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Liang Li
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Min Ma
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Zhijian Chen
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Guojiang Tan
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Ning Yin
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Chonglei Zhong
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Bowen Yu
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Yihang Guo
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Miao Chen
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Gui Hu
Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Corresponding author
Summary: CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1.
