Oncotarget

Research Papers:

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

Wenhui Ma _, Jiang Yu, Xiaolong Qi, Li Liang, Yan Zhang, Yi Ding, Xiaoshan Lin, Guoxin Li and Yanqing Ding

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Oncotarget. 2015; 6:15984-15994. https://doi.org/10.18632/oncotarget.3762

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Abstract

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

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.


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