MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma.
To obtain microRNA (miRNA) profile and clarify their biological function in tumorigenic Sca-1(+) CD34(+) cells during carcinogenesis of lung adenocarcinoma. After intranasal infection with recombinant Adeno-Cre viruses (AdV-Cre), lung adenocarcinoma was identified pathologically in Lox-stop-lox Kras (LSL-Kras) G12D mice. Sca-1(+) CD34(+) cells were sorted by flow cytometry and tested for tumor-initiating ability, self-renewal and tumorigenicity. MiRNA profiles were obtained using microarray and further confirmed by real-time RT-PCR (qRT-PCR). MiRNA functions were predicted bioinformatically, and miR-294 function was verified to explore its role in tumor migration and invasion. Lung adenocarcinoma was induced in LSL-Kras G12D mice within 30 days. In vivo, the tumorigenicity of Sca-1(+) CD34(+) cells was 25 times stronger than Sca-1(-) CD34(-) cells. During tumorigenesis of lung adenocarcinoma, the expression of 145 miRNAs in Sca-1(+) CD34(+) cells increased and 72 miRNAs decreased (P < 0.01). Four successively up-regulated miRNAs (miR-15a*, miR-203, miR-294 and miR-295*) and three successively down-regulated ones (miR-19b, miR-483 and miR-615-5p) were identified. Among them, miR-294 could constitutively bind to 3'-UTR of matrix metalloproteinase 3 (MMP3), and down-regulate MMP3 protein expression. MiR-294 also significantly inhibited migration and invasion of Lewis lung cancer cells. MiRNAs are characteristically expressed in tumor-initiating Sca-1(+) CD34(+) cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma.
['Zhao|Zhen-guo|ZG|', 'Jin|Jun-yu|JY|', 'Zhang|An-mei|AM|', 'Zhang|Lu-ping|LP|', 'Wang|Xin-xin|XX|', 'Sun|Jian-guo|JG|', 'Chen|Zheng-tang|ZT|']
D000230:Adenocarcinoma D000077192:Adenocarcinoma of Lung D000818:Animals D018952:Antigens, CD34 D000950:Antigens, Ly D063646:Carcinogenesis D018827:Carcinoma, Lewis Lung D049109:Cell Proliferation D002469:Cell Separation D004195:Disease Models, Animal D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D057809:HEK293 Cells D006801:Humans D008175:Lung Neoplasms D008565:Membrane Proteins D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D014411:Neoplastic Stem Cells D015203:Reproducibility of Results
TUMORIGENIC CELLS CARCINOGENESIS LUNG ADENOCARCINOMA miRNAs