Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells.
Increasing evidence suggests that microRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. A growing number of reports has shown that an interest has been sparked in aberrant microRNA expression and how they can be used to treat human diseases, including cancer. However, their precise biological role remains largely unknown. In the present study, we aimed to identify micro-RNA species involved in the regulation of tumor growth. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that mir-663 was downregulated in human gastric cancer cell lines unlike in normal cells. A transient introduction of mir-663 into the human gastric cancer cell lines BGC823 and SNU5 induced morphology changes and suppression of proliferation of these cells. In addition, mir-663 alters the DNA content and induces phenotypes of mitotic catastrophe in tumor cells. Moreover, the liposome-mediated delivery of mir-663 suppressed the in vivo growth of the BGC823 and SNU5 cells. Western blot analyses performed after the introduction of mir-663 revealed upregulation of cyclin B following transfection with mir-663. Our results provide evidence that downregulation of mir-663 in tumor cells may contribute to aberrant cell hyperplasia, leading to the development of gastric cancer. Therefore, mir-663 might function as a potent suppressor of tumor growth.
The State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, PR China.
Jian
J
Pan
Hai
H
Hu
Zhuan
Z
Zhou
Lichao
L
Sun
Liang
L
Peng
Long
L
Yu
Lixin
L
Sun
Jun
J
Liu
Zhihua
Z
Yang
Yuliang
Y
Ran
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy
D004273:DNA, Neoplasm; C552243:MIRN663 microRNA, human; D035683:MicroRNAs