Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression.

Weiqun Lu,Nanrong Yu,Jianchang Li,Shicai Chen,Guohua Yang,Jia Wang,Haiying Liu,Jiliang Qiu,Houwei Xu,Zhiliang Huang,Xiang Zeng,Nan Li

doi:10.18632/oncotarget.14839

Weiqun Lu, Nanrong Yu + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.14839

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Journal: Oncotarget	Publication Date: Jan 27, 2017
Citations: 39	License type: cc-by

Affiliation: Guangzhou Medical University

Abstract

Here we demonstrated that Galectin-3 protein level was frequently up-regulated in colorectal cancer (CRC) cells and tissues. Galectin-3 up-regulation correlated with CRC progression and predicted a shorter overall survival of CRC patients. Galectin-3 overexpression attenuated the chemo-sensitivity of cancer cells, but enhanced the potential invasiveness. To explore the mechanism for Galectin-3 dysregulation, we found that miR-128 level was frequently down-regulated in CRC and negatively correlated with Galectin-3 level. Using bioinformatics analysis and experimental validation, we showed that miR-128 could directly target Galectin-3 to repress its protein level. MiR-128 decrease associated with CRC progression and predicted a worse overall survival of CRC patients. Ectopic miR-128 expression enhanced the chemo-sensitivity of CRC cells in vitro and in vivo, and inhibited the potential invasiveness. Galectin-3 expression impaired the cancer suppressive effects of miR-128. These data highlighted the role of miR-128/Galectin-3 axis in colorectal cancer.

Highlights

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States, with an estimated 136,830 new cases and 50,310 deaths in 2014 [1]
We found that compared to levels in Hela cells, all ten colorectal cancer (CRC) cell lines possessed relatively high protein level of Galectin-3, but not mRNA level (Figure 1A)
CRC patients with high Galectin-3 levels had poor overall survival times (Figure 1C). These results indicated that Galectin-3 was overexpressed in CRC, and was a potential poor prognostic marker for CRC patients

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States, with an estimated 136,830 new cases and 50,310 deaths in 2014 [1]. Despite of early screening and development of new chemotherapeutic strategies, the CRC survival rates during the past 20 years have not substantially improved. The five-year survival rate for metastatic colon cancer is still less than 10%. Limited sensitivity to chemotherapy and metastasis are the most frequent reasons of treatment failure [2]. It is critical to understand the mechanisms for chemo-insensitivity and metastasis, and to identify potential therapeutic targets to improve patients’ outcomes. Galectin-3 exhibits pleiotropic biological and molecular functions via both extracellular and intracellular manners. Galectin-3 interacts with cell surface and extracellular matrix glycoproteins and glycolipids to adjust microenvironment

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