Abnormal Expression of miR-21 and miR-95 in Cancer Stem-Like Cells is Associated with Radioresistance of Lung Cancer

This study demonstrated that miR-21 and miR-95 expression were significantly higher in the ALDH1+CD133+subpopulation than in the ALDH1 CD133 subpopulation of lung cancer cells. Combined delivery of anti-miR-21 and anti-miR-95 by calcium phosphate nanoparticles significantly inhibited tumor growth in...

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Bibliographic Details
Published in:Cancer investigation 2015-05, Vol.33 (5), p.165-171
Main Authors: Zhang, Jinghui, Zhang, Chailan, Hu, Lin, He, Yin, Shi, Zeya, Tang, Siyuan, Chen, Yuxiang
Format: Article
Language:English
Subjects:
AC133 Antigen
Antigens, CD - genetics
cancer stem cell
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Proliferation - drug effects
Cell Proliferation - genetics
Gene Expression Regulation, Neoplastic
Glycoproteins - genetics
H1299
Humans
Isoenzymes - genetics
Lung Cancer
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Membrane Proteins - biosynthesis
MicroRNAs - antagonists & inhibitors
MicroRNAs - biosynthesis
miRNA
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - pathology
Peptides - genetics
Phosphoric Monoester Hydrolases - biosynthesis
PTEN Phosphohydrolase - biosynthesis
Radiation Tolerance - genetics
Radioresistance
Retinal Dehydrogenase - genetics
RNA, Antisense - administration & dosage
Sorting Nexins - biosynthesis
Xenograft Model Antitumor Assays
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Summary:This study demonstrated that miR-21 and miR-95 expression were significantly higher in the ALDH1+CD133+subpopulation than in the ALDH1 CD133 subpopulation of lung cancer cells. Combined delivery of anti-miR-21 and anti-miR-95 by calcium phosphate nanoparticles significantly inhibited tumor growth in a xenograft tumor model and sensitized radiotherapy. The anti-miRNAs significantly reduced miR-21 and miR-95 levels, increased PTEN, SNX1, and SGPP1 protein expression, but reduced Akt Ser473 and Thr308 phosphorylation. ALDH1+CD133+ subpopulation of NSCLC tumor cells confers radioresistance due to high expression of miR-21 and miR-95. Targeting inhibition of miR-21 and miR-95 can inhibit tumor growth through elevating PTEN, SNX1, and SGPP1 expression and inhibiting Akt phosphorylation.
ISSN:0735-7907
1532-4192
DOI:10.3109/07357907.2015.1019676