International Journal of Nanomedicine (Jun 2022)

Systematic Identification of Genomic Markers for Guiding Iron Oxide Nanoparticles in Cervical Cancer Based on Translational Bioinformatics

  • Zhou H,
  • Tian J,
  • Sun H,
  • Fu J,
  • Lin N,
  • Yuan D,
  • Zhou L,
  • Xia M,
  • Sun L

Journal volume & issue
Vol. Volume 17
pp. 2823 – 2841

Abstract

Read online

Haohan Zhou,1,2,* Jiayi Tian,3,* Hongyu Sun,1 Jiaying Fu,1 Nan Lin,1 Danni Yuan,1 Li Zhou,3 Meihui Xia,3 Liankun Sun1 1Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, 200000, People’s Republic of China; 3First Hospital, Jilin University, Changchun, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liankun Sun, Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, People’s Republic of China, Email [email protected] Meihui Xia, First Hospital, Jilin University, Changchun, 130021, People’s Republic of China, Email [email protected]: Magnetic iron oxide nanoparticle (MNP) drug delivery system is a novel promising therapeutic option for cancer treatment. Material issues such as fabrication and functionalized modification have been investigated; however, pharmacologic mechanisms of bare MNPs inside cancer cells remain obscure. This study aimed to explore a systems pharmacology approach to understand the reaction of the whole cell to MNPs and suggest drug selection in MNP delivery systems to exert synergetic or additive anti-cancer effects.Methods: HeLa and SiHa cell lines were used to estimate the properties of bare MNPs in cervical cancer through 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and enzyme activity assays and cellular fluorescence imaging. A systems pharmacology approach was utilized by combining bioinformatics data mining with clinical data analysis and without a predefined hypothesis. Key genes of the MNP onco-pharmacologic mechanism in cervical cancer were identified and further validated through transcriptome analysis with quantitative reverse transcription PCR (qRT-PCR).Results: Low cytotoxic activity and cell internalization of MNP in HeLa and SiHa cells were observed. Lysosomal function was found to be impaired after MNP treatment. Protein tyrosine kinase 2 beta (PTK2B), liprin-alpha-4 (PPFIA4), mothers against decapentaplegic homolog 7 (SMAD7), and interleukin (IL) 1B were identified as key genes relevant for MNP pharmacology, clinical features, somatic mutation, and immune infiltration. The four key genes also exhibited significant correlations with the lysosome gene set. The qRT-PCR results showed significant alterations in the expression of the four key genes after MNP treatment in HeLa and SiHa cells.Conclusion: Our research suggests that treatment of bare MNPs in HeLa and SiHa cells induced significant expression changes in PTK2B, PPFIA4, SMAD7, and IL1B, which play crucial roles in cervical cancer development and progression. Interactions of the key genes with specific anti-cancer drugs must be considered in the rational design of MNP drug delivery systems.Keywords: drug delivery, anti-cancer drugs, PTK2B, PPFIA4, SMAD7, IL1B

Keywords