Theranostics 2014; 4(12):1193-1208. doi:10.7150/thno.8712
MiR-194 Deregulation Contributes To Colorectal Carcinogenesis via Targeting AKT2 Pathway
1. State Key Laboratory for Oncogenes and Related Genes Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Diseases, 145 Middle Shandong Road, Shanghai 200001, China.
2. Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
3. Key Lab in Healthy Science and Technology; Division of Life Science; Graduate School at Shenzhen; Tsinghua University; Shenzhen, China.
* The three authors contributed equally to this work.
Abstract: Recent studies have increasingly linked microRNAs to colorectal cancer (CRC). MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored. Here we investigated the biological effects, mechanisms and clinical significance of miR-194. Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo. Conversely, block of miR-194 in APCMin/+ mice promoted tumor growth. Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo. Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression. Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases. Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006), lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009). In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC.
Keywords: colorectal cancer, miR-194, AKT2 pathway, biomarker, carcinogenesis.
Zhao HJ, Ren LL, Wang ZH, Sun TT, Yu YN, Wang YC, Yan TT, Zou W, He J, Zhang Y, Hong J, Fang JY. MiR-194 Deregulation Contributes To Colorectal Carcinogenesis via Targeting AKT2 Pathway. Theranostics 2014; 4(12):1193-1208. doi:10.7150/thno.8712. Available from http://www.thno.org/v04p1193.htm