MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2.
MicroRNAs have been suggested to play a vital role in regulate tumor progression and invasion. However, the expression of miR-335 in colorectal cancer (CRC) and its clinical significance are not known. Here, we report that miR-335 is a tumor suppressor by regulating expression of ZEB2. In this study, we showed that downregulated miR-335 levels in highly invasive CRC cell lines and tissues. Kaplan-Meier survival analysis indicated that patients with reduced miR-335 had a poor overall survival. Furthermore, enhancing the expression of miR-335 inhibited CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in increased migration and invasion. Additionally, we identified a novel miR-335 target, ZEB2, and the direct interaction between them was verified by 3'-untranslated region dual-luciferase reporter assay. In conclusion, our results demonstrate that miR-335 functions as a tumor suppressor and play a role in inhibiting metastasis of CRC cells through targeting ZEB2. These findings suggest that miR-335 may be useful as a new potential therapeutic target for CRC.
Department of Gastrointestinal Surgery, Xi Jing Digestive Hospital, Fourth Military Medical University, Xi'an, Shan Xi Province, China.
ZhiFeng
Z
Sun
Zhang
Z
Zhang
Zidong
Z
Liu
Bo
B
Qiu
Kan
K
Liu
Guanglong
G
Dong
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D000074165:Zinc Finger E-box Binding Homeobox 2
D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2