Tumor Biology

, Volume 37, Issue 1, pp 521–530 | Cite as

Identification of carcinogenic potential-associated molecular mechanisms in CD133+ A549 cells based on microRNA profiles

Research Article

Abstract

This study aimed to identify carcinogenic potential-related molecular mechanisms in cancer stem cells (CSCs) in lung cancer. CD133+ and CD133 subpopulations were sorted from A549 cells using magnetic-activated cell sorting. The abilities to form sphere and clone, proliferate, migrate, and invade were compared between CD133+ and CD133 cells, as well as drug sensitivity. Thereafter, microRNA (miRNA) profiles were performed to identify differentially expressed miRNAs between CD133+ and CD133 subpopulation. Following, bioinformatic methods were used to predict target genes for differentially expressed miRNAs and perform enrichment analysis. Furthermore, the mammalian target of rapamycin (mTOR) signaling pathways and CSC property-associated signaling pathways were explored and visualized in regulatory network among competitive endogenous RNA (ceRNA), miRNA, and target gene. CD133+ subpopulation showed greater oncogenic potential than CD133 subpopulation. In all, 14 differentially expressed miRNAs were obtained and enriched in 119 pathways, including five upregulated (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, and -4734) and nine downregulated (hsa-miR-1246, -30b-5p, -5096, -6510-5p, has-miR-7110-5p, -7641, -3197, -7108-5p, and -6791-5p). For mTOR signaling pathway, eight differential miRNAs (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, -4734, -1246, -7641, and -3197) and 39 target genes (e.g., AKT1, AKT2, PIK3CB, PIK3CG, PIK3R1, PIK3CA, and PIK3CD) were involved, as well as some ceRNAs. Besides, for CSC property-related signaling pathways, six miRNAs (hsa-miR-1246, -15b-5p, -30b-5p, -3197, -4734, and -7110-5p) were dramatically enriched in Hedgehog, Notch, and Wnt signaling pathways via regulating 108 target genes (e.g., DVL1, DVL3, WNT3A, and WNT5A). The mTOR and CSC property-associated signaling pathways may be important oncogenic molecular mechanisms in CD133+ A549 cells.

Keywords

Non-small cell lung cancer Cancer stem cell CD133 mTOR MicroRNA profile Bioinformatic methods 

Notes

Acknowledgments

This study was supported by “334” High-tech Talent Training Program of Nanjing Military Command and Natural Science Foundation of Zhejiang Province of China (LY12H16001).

Conflicts of interest

None

Supplementary material

13277_2015_3675_Fig5_ESM.gif (16 kb)
Supplementary Fig. 1

CD133 expression checked by flow cytometry. a, CD133 expression of harvested cells before magnetic activated cell sorting; b, CD133 expression of CD133+ fractions after magnetic activated cell sorting. (GIF 15 kb)

13277_2015_3675_MOESM1_ESM.tif (523 kb)
(TIFF 522 KB)
13277_2015_3675_Fig6_ESM.gif (47 kb)
Supplementary Fig. 2

Network of differentially expressed miRNA and CD133 (PROM1). Red circle represents target gene, and green triangle represents differentially expressed miRNA. miRNA, microRNA. (GIF 46 kb)

13277_2015_3675_MOESM2_ESM.tif (159 kb)
(TIFF 159 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  2. 2.Department of Respiratory DiseaseThe 117th Hospital of PLAHangzhouPeople’s Republic of China
  3. 3.Department of OncologyThe 117th Hospital of PLAHangzhouPeople’s Republic of China

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