Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells by down-regulating Rb
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Wenhui Ma1,*, Jiang Yu1,2,*, Xiaolong Qi3,5,*, Li Liang2, Yan Zhang1, Yi Ding4, Xiaoshan Lin4, Guoxin Li1, Yanqing Ding2
1Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
2Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China
3Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
4Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
5Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
*These authors have contributed equally to this work
Yanqing Ding, e-mail: firstname.lastname@example.org
Guoxin Li, e-mail: email@example.com
Keywords: radiosensitivity, microRNA-622, apoptosis, RB1, Rb
Received: January 16, 2015 Accepted: April 06, 2015 Published: April 18, 2015
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.
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