title: NLK, a novel target of miR-199a-3p, functions as a tumor suppressor in colorectal cancer.
abstract: We previously reported that miR-199a-3p is a newly biomarker for diagnosis and novel prognostic indicator in colorectal cancer. However, the miR-199a-3p regulatory mechanism and its target genes are still unclear. In our present study, we demonstrated miR-199a-3p could directly target 3'-UTR of NLK gene by luciferase reporter assay and western blot analysis. We detected NLK expressions in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. Our results showed that NLK expression was significantly downregulated in cancer tissues than NATs, and NLK low-expression was associated with lymph node metastasis, venous invasion, liver metastasis and the TNM stage (P<0.05). Moreover, Kaplan-Meier analysis showed that low expression of NLK correlated with a shorter overall survival rates of patients with CRC (P<0.05). In vitro, we also found that NLK suppressed the biological behaviors of colorectal cancer cells, including the abilities of cell proliferation, clone formation, wound healing, migration and invasion (P<0.05), while overexpression of NLK increased the apoptotic rate of colorectal cancer cells. All these results suggested that NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer. NLK could be a novel direction for developing diagnostic and therapeutic approaches in colorectal cancer.
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Ye
authors: Y
authors: Han
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Yuting
authors: Y
authors: Kuang
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Xiaofeng
authors: X
authors: Xue
authors: Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors: Xiaobo
authors: X
authors: Guo
authors: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors: Pu
authors: P
authors: Li
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Xu
authors: X
authors: Wang
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Xingpo
authors: X
authors: Guo
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Bin
authors: B
authors: Yuan
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: strexboy@163.com.
authors: Qiaoming
authors: Q
authors: Zhi
authors: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: zhaohong600@sina.com.
authors: Hong
authors: H
authors: Zhao
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013194:Staining and Labeling; D015996:Survival Rate; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; C531408:mirn199 microRNA, human; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Colorectal cancer; MiR-199a-3p; NLK; Tumor suppressor