PMID- 25359683 OWN - NLM STAT- MEDLINE DCOM- 20150917 LR - 20190221 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 116 IP - 3 DP - 2015 Mar TI - MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma. PG - 458-66 LID - 10.1002/jcb.24999 [doi] AB - 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. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Zhao, Zhen-guo AU - Zhao ZG AD - Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China. FAU - Jin, Jun-yu AU - Jin JY FAU - Zhang, An-mei AU - Zhang AM FAU - Zhang, Lu-ping AU - Zhang LP FAU - Wang, Xin-xin AU - Wang XX FAU - Sun, Jian-guo AU - Sun JG FAU - Chen, Zheng-tang AU - Chen ZT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Antigens, CD34) RN - 0 (Antigens, Ly) RN - 0 (Ly6a protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) SB - IM ECI - J Cell Biochem. 2015 Sep;116(9):2120. PMID: 26205483 MH - Adenocarcinoma/*genetics/pathology MH - Adenocarcinoma of Lung MH - Animals MH - Antigens, CD34/metabolism MH - Antigens, Ly/metabolism MH - Carcinogenesis/*genetics/pathology MH - Carcinoma, Lewis Lung/genetics/pathology MH - Cell Proliferation MH - Cell Separation MH - Disease Models, Animal MH - *Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - HEK293 Cells MH - Humans MH - Lung Neoplasms/*genetics/pathology MH - Membrane Proteins/metabolism MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/genetics/*metabolism MH - Neoplastic Stem Cells/metabolism/pathology MH - Reproducibility of Results OTO - NOTNLM OT - CARCINOGENESIS OT - LUNG ADENOCARCINOMA OT - TUMORIGENIC CELLS OT - miRNAs EDAT- 2014/11/02 06:00 MHDA- 2015/09/18 06:00 CRDT- 2014/11/01 06:00 PHST- 2014/05/10 00:00 [received] PHST- 2014/10/20 00:00 [accepted] PHST- 2014/11/01 06:00 [entrez] PHST- 2014/11/02 06:00 [pubmed] PHST- 2015/09/18 06:00 [medline] AID - 10.1002/jcb.24999 [doi] PST - ppublish SO - J Cell Biochem. 2015 Mar;116(3):458-66. doi: 10.1002/jcb.24999.