Research Papers:

miRNA-99b-5p suppresses liver metastasis of colorectal cancer by down-regulating mTOR

Wenhua Li, Jinjia Chang, Shanshan Wang, Xinyang Liu, Junjie Peng, Dan Huang, Menghong Sun, Zhiyu Chen, Wen Zhang, Weijian Guo, Jin Li _

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Wenhua Li1,2,*, Jinjia Chang1,2,*, Shanshan Wang1,2, Xinyang Liu1,2, Junjie Peng2,3, Dan Huang2,4, Menghong Sun2,4, Zhiyu Chen1,2, Wen Zhang1,2, Weijian Guo1,2 and Jin Li1,2

1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

3 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

4 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Jin Li, email:

Keywords: colorectal carcinoma, liver metastasis, miR-99b-5p, mTOR

Received: February 28, 2015 Accepted: May 30, 2015 Published: June 10, 2015


Liver metastasis is common in patients diagnosed with colorectal cancer (CRC), and is also correlated with poor outcome. In this study we screened the different expression profiles of microRNAs (miRNAs) on the development of liver metastasis in CRC patients. miR-99b-5p was found to be more than 6-fold higher in primary tumors than in matched liver metastases (P = 0.007). Expression of miR-99b-5p in primary tumors of patients with stage III CRC without liver metastases was higher than in CRC patients with liver metastases (P = 0.028). Up-regulated miR-99b-5p was associated with longer overall survival (P = 0.01). Besides, miR-99b-5p silencing in miR-99b-5p-positive CRC cell lines promoted cell migration and up-regulated mTOR, and vice versa. In addition, luciferase assays demonstrated that miR-99b-5p functioned as a tumor suppressor by targeting mTOR. Taken together, our results demonstrate thatmiR-99b-5p is differently expressed in primary CRC and liver metastasis and functions as a tumor-suppressive microRNA in metastatic CRC. The miR-99b-5p–mTOR axis may serve as a prognostic factor and therapeutic target for anti-metastatic therapy in CRC patients.

Author Information

Wenhua Li

Jinjia Chang

Shanshan Wang

Xinyang Liu

Junjie Peng

Dan Huang

Menghong Sun

Zhiyu Chen

Wen Zhang

Weijian Guo

Jin Li
Primary Contact  _

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