Oncotarget

Research Papers:

miR-29a-3p suppresses cell proliferation and migration by downregulating IGF1R in hepatocellular carcinoma

Xiao Wang, Shasha Liu, Ling Cao, Tengfei Zhang, Dongli Yue, Liping Wang, Yu Ping, Qianyi He, Chaoqi Zhang, Meng Wang, Xinfeng Chen, Qun Gao, Dan Wang, Zhen Zhang, Fei Wang, Li Yang, Jieyao Li, Lan Huang, Bin Zhang and Yi Zhang _

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Oncotarget. 2017; 8:86592-86603. https://doi.org/10.18632/oncotarget.21246

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Abstract

Xiao Wang1,2, Shasha Liu1,3, Ling Cao1,2, Tengfei Zhang1, Dongli Yue1,2, Liping Wang2, Yu Ping1,3, Qianyi He2, Chaoqi Zhang1,2, Meng Wang1, Xinfeng Chen1,2, Qun Gao1,2, Dan Wang1,2, Zhen Zhang1, Fei Wang1, Li Yang1, Jieyao Li1,2, Lan Huang1, Bin Zhang4 and Yi Zhang1,2,3,5

1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China

2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China

3School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China

4Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, IL 60611, USA

5Key Laboratory for Tumor Immunology and Biotherapy of Henan Province, Zhengzhou, Henan 450052, P.R. China

Correspondence to:

Yi Zhang, email: yizhang@zzu.edu.cn

Keywords: miR-29a-3p, IGF1R, hepatocellular carcinoma, proliferation, CCL5

Received: July 06, 2017     Accepted: August 23, 2017     Published: September 23, 2017

ABSTRACT

Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein that has been reported to promote transformation to malignancy and cancer cell proliferation and survival. In this study, we found that the expression of miR-29a-3p was downregulated in HCC patients, resulting in poor survival rates. Contrastingly, the overexpression of miR-29a-3p significantly inhibited proliferation and migration in HepG2 cells. miR-29a-3p directly targeted IGF1R and down-regulated its expression. Moreover, knockdown of IGF1R led to the increased production of chemokine ligand 5 (CCL5). In tumor lesions, the local expression of CCL5 negatively affected the expression of IGF1R. Transwell analysis showed that CCL5 was important for the chemotactic movement of CD8+ T lymphocytes. The expression of CCL5 in HCC tissues positively correlated with the expression of CD8+ T lymphocyte surface marker, CD8. Patients with high CCL5 expression exhibited better survival. Our results revealed that miR-29a-3p is a tumor suppressor gene that acts by directly repressing the oncogene IGF1R, which takes part in immunoregulation in tumor microenvironments in HCC, implying that miR-29a-3p could be a potential target for HCC treatment.


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