J Cancer 2019; 10(15):3560-3570. doi:10.7150/jca.28272

Research Paper

MiR-506 Suppresses Colorectal Cancer Development by Inhibiting Orphan Nuclear Receptor NR4A1 Expression

Meihui Huang1,2*, Xina Xie1,3*, Xuhong Song1, Songgang Gu4, Xiaolan Chang1, Ting Su1, Bin Liang1✉, Dongyang Huang1✉

1. Department of Cell Biology and Genetics and Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou 515041, China.
2. Department of Pathology and Central Laboratory, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, China.
3. Institute of Translational Medicine, Shenzhen Second People's Hospital, the First Affiliated H-ospital of Shenzhen University, Health Science Center, Shenzhen 518035, China.
4. Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
* Equal Contributors

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Citation:
Huang M, Xie X, Song X, Gu S, Chang X, Su T, Liang B, Huang D. MiR-506 Suppresses Colorectal Cancer Development by Inhibiting Orphan Nuclear Receptor NR4A1 Expression. J Cancer 2019; 10(15):3560-3570. doi:10.7150/jca.28272. Available from http://www.jcancer.org/v10p3560.htm

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Abstract

NR4A1 acts as an oncogene and plays an important role in colorectal cancer development and progression, but little is known about the regulatory mechanism of NR4A1 expression. MicroRNA (miRNA) is involved in the progression of various tumors, affecting proliferation, apoptosis or migration. We aimed to elucidate whether miRNA regulates NR4A1 expression and determine its underlying significance in colorectal cancer. By using the TargetScan database, we identified a miR-506 binding site in the NR4A1 3'-UTR. Examination of colorectal cancer tissues and cells revealed that NR4A1 mRNA and protein were up-regulated, while miR-506 expression was down-regulated. Spearman correlation analysis revealed that expression of NR4A1 mRNA was negatively correlated with miR-506 levels in colorectal cancer tissue. Further studies indicated that miR-506 decreased NR4A1 expression through directly targeting the NR4A1 mRNA 3'-UTR. Functional experiments showed that rescue of NR4A1 expression in cells reversed the inhibitory effects of miR-506 on proliferation, migration and invasion of colorectal cancer cells. In conclusion, miR-506 acts as a tumor suppressor and inhibits proliferation, migration and invasion in colorectal cancer cells partly through decreasing NR4A1 expression.

Keywords: Colorectal cancer, NR4A1, MiR-506, Proliferation, Migration, Invasion