Research Papers:

Insulin-like growth factor-I induces chemoresistence to docetaxel by inhibiting miR-143 in human prostate cancer

Xiao-Bing Niu, Guang-Bo Fu, Lin Wang, Xin Ge, Wei-Tao Liu, Yi-Yang Wen, Hao-Ran Sun, Ling-Zhi Liu, Zeng-Jun Wang and Bing-Hua Jiang _

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Oncotarget. 2017; 8:107157-107166. https://doi.org/10.18632/oncotarget.22362

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Xiao-Bing Niu1,2,3*, Guang-Bo Fu1,3,* Lin Wang4,*, Xin Ge1, Wei-Tao Liu1, Yi-Yang Wen1, Hao-Ran Sun1, Ling-Zhi Liu5, Zeng-Jun Wang2 and Bing-Hua Jiang1,5

1State Key Laboratory of Reproductive Medicine, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China

2Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

3Department of Urology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

4Institute of Medical and Pharmaceutical Sciences, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China

5Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA

*These authors have contributed equally to this work

Correspondence to:

Bing-Hua Jiang, email: [email protected]

Zeng-Jun Wang, email: [email protected]

Keywords: prostate cancer; docetaxel; miR-143; IGF-I; tumor growth

Received: January 31, 2017     Accepted: September 15, 2017     Published: November 09, 2017


Elevated levels of insulin-like growth factor-I (IGF-I) are associated with carcinogenesis and cancer progression. However, the molecular mechanisms by which IGF-I promotes prostate cancer development remain to be elucidated. Docetaxel chemotherapy is an important therapeutic strategy in many types of human cancers including prostate cancer. In this study, we showed that IGF-I rendered PC-3 and DU145 cells more resistant to docetaxel treatment. IGF-I treatment decreased miR-143 expression, but increased the expression levels of IGF-I receptor (IGF-IR) and insulin receptor substrate 1 (IRS1), direct targets of miR-143. Overexpression of miR-143 abolished IGF-I-induced chemoresistance to docetaxel treatment, decreased expression levels of IGF-I, IRS1, and vascular endothelial growth factor (VEGF) in prostate cancer cell lines. Furthermore, docetaxel treatment significantly inhibited VEGF transcriptional activation, whereas IGF-I treatment induced VEGF transcriptional activation in a dose-dependent manner. Forced expression of IGF-IR and IRS1 cDNAs without the 3’ UTR regions restored miR-143-inhibited VEGF transcriptional activation. Finally, miR-143 inhibited tumor growth and made cells more sensitive to docetaxel treatment for decreasing tumor growth in vivo. Taken together, our data demonstrates that IGF-I induces docetaxel resistance and upregulates IGF-IR and IRS1 expression through miR-143 downregulation, whereas miR-143 acts as a tumor suppressor by targeting its targets IGF-IR and IRS1.

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