Lentiviral vector-mediated upregulation of let-7a inhibits gastric carcinoma cell growth in vitro and in vivo.
OBJECTIVE
Let-7a, a molecule that is reduced in various cancers, has been associated with cell growth and proliferation. Upregulation of let-7a may inhibit tumor cell growth. To verify this hypothesis, let-7a gene overexpression was studied in gastric cancer cells in vitro and in vivo.


METHODS
A lentiviral system harboring both enhanced green fluorescent protein reporter gene and the let-7a short hairpin RNA expression cassette was firstly constructed. Then the stable let-7a gene overexpression SGC-7901 cells were established and real-time RT-PCR analysis was used to evaluate the expression of the let-7a gene. Their growth-inhibiting, cell cycle arrest characteristics were identified.


RESULTS
In SGC-7901/let-7a cells, let-7a expression was significantly increased. Their proliferation was obviously retarded and the cell cycle changed with increased G0/G1 arrest and decreased S phase. In animal experiments, SGC-7901/let-7a cell xenografts demonstrated growth suppression compared to parental or control gastric cancer cell xenografts.


CONCLUSIONS
The results demonstrated that lentiviral vector was capable of upregulating let-7a, resulting in impressive anticancer effects. It offers a powerful new strategy for the development of novel therapeutic interventions to treat human gastric carcinomas.
Zhu
Yimin
Y
Department of General Surgery, The Second Hospital of Jiaxing, Jiaxing, PR China.
Zhong
Zhengxiang
Z
Liu
Zhiming
Z
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D035683:MicroRNAs; C487931:mirnlet7 microRNA, human