Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells by down-regulating Rb

// Wenhui Ma 1, * , Jiang Yu 1, 2, * , Xiaolong Qi 3, 5, * , Li Liang 2 , Yan Zhang 1 , Yi Ding 4 , Xiaoshan Lin 4 , Guoxin Li 1 , Yanqing Ding 2 1 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China 3 Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA 4 Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China 5 Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Yanqing Ding, e-mail: dyqgz@126.com Guoxin Li, e-mail: gzliguoxin@163.com Keywords: radiosensitivity, microRNA-622, apoptosis, RB1, Rb Received: January 16, 2015      Accepted: April 06, 2015      Published: April 18, 2015 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.