title: Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells by down-regulating Rb.
abstract: The standard treatment for patients with locally advanced rectal cancer is preoperative 5-fluorouracil-based chemoradiotherapy followed by total mesorectal excision. However, tumor response to standard dose radiation varies. In this study, we found that miR-622 was increased significantly in ionizing radiation-treated colorectal cancer (CRC) cells compared to the cells cultured with irradiated medium, and persisted stably in surviving cells treated with continuous low-dose radiation. Overexpression of miR-622 induced the radioresistance in vitro. In addition, miR-622 inhibited Rb expression by directly targeting RB1-3'UTR. Overexpression of Rb reversed miR-622-induced radioresistance in vitro. In response to ionizing radiation, the Rb-E2F1-P/CAF complex activated proapoptotic genes. Importantly, miR-622 was highly expressed in tumors of rectal cancer patients with non-regression after standard dose radiotherapy. In conclusion, miR-622 overexpressing cells are induced or selected by radiotherapy, causing in turn radioresistance and poor response to further therapy. MiR-622 is a potential biomarker of responders for radiotherapy and a potential therapeutic target.
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015536:Down-Regulation / Q000528:radiation effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011836:Radiation Tolerance; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
chemical_list: C560103:MIRN622 microRNA, human; D035683:MicroRNAs; D016160:Retinoblastoma Protein
keywords: RB1; Rb; apoptosis; microRNA-622; radiosensitivity