Circulating miRNAs could be good biomarkers for cancers because miRNAs regulate gene expression and thus are related to cancer initiation and development. They are easy to detect, and sampling blood or serum is considered non-invasive and simple to implement. However, there is a long way to go before reproducible and reliable biomarkers can be applied in clinical diagnosis. Large variations in miRNA expression levels among individuals, in sample handling, in miRNA extraction and detection techniques, etc., all contribute to the extremely poor agreements between the circulating miRNA signatures reported by different research groups. The recent discovery of different miRNA carriers, i.e. proteins, high density lipoprotein (HDL) particles, and exosomes, in the circulation system suggests that maybe only a particular type of miRNAs is relevant to cancers; however, it is still not known which will be the killer type. Hence, we propose to examine the 3-dimensional expression profiles of miRNAs, which will provide information about distribution of miRNAs among different groups of carriers. A separation method will be developed to fractionate miRNAs associated with different types of carriers in a rapid, high-throughput, and semi-automatic manner. Such an approach will significantly reduce variations in miRNA handling and extraction. By comparing the distribution profiles collected from healthy controls and cancer patients, distinct changes in the relative contents of miRNAs within different types of carriers in patients' sera will be identified, which will be useful for cancer detection. Proper internal controls for normalizing miRNA contents in different individuals, and in samples handled and/or stored under different conditions will also be identified. Furthermore, a microchip device that highly simplifies the fractionation process will assist with biomarker validation in a large number of patients' sera samples. The final deliverables of the proposed research will be specific, sensitive, and reliable biomarkers for early cancer detection. Evaluation of these markers will also be simple enough to be carried out in regular clinical labs to help more patients battle with cancers and increase the survival rates by capturing the signal of cancer development at the early stage.

Public Health Relevance

Experiments have been proposed to test the hypothesis that, the distribution profiles of circulating miRNAs among different carriers are sensitive and specific at detecting cancers at early stages. Besides the discovery of the highly specific and sensitive miRNA biomarkers for cancer diagnosis, knowing what are carriers for the circulating miRNAs highly relevant to cancer initiation and development can lead to better understanding of the secretion and transportation mechanism of the circulating miRNAs can be achieved. Both outcomes will make significant contribution to the improvement of public health and the enhancement of cancer survival rates.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA188991-03S1
Application #
9379093
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Schwartz, Elena Ivan
Project Start
2015-04-23
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2017
Total Cost
$29,963
Indirect Cost
$7,108
Name
University of California Riverside
Department
Chemistry
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Shen, Wen; Guo, Kaizhu; Adkins, Gary Brent et al. (2018) A Single Extracellular Vesicle (EV) Flow Cytometry Approach to Reveal EV Heterogeneity. Angew Chem Int Ed Engl 57:15675-15680
Fang, Xiaoni; Duan, Yaokai; Adkins, Gary Brent et al. (2018) Highly Efficient Exosome Isolation and Protein Analysis by an Integrated Nanomaterial-Based Platform. Anal Chem 90:2787-2795
Jimenez, Luis A; Gionet-Gonzales, Marissa A; Sedano, Sabrina et al. (2018) Extraction of microRNAs from biological matrices with titanium dioxide nanofibers. Anal Bioanal Chem 410:1053-1060
Fang, Xiaoni; Liu, Yang; Jimenez, Luis et al. (2017) Rapid Enrichment and Sensitive Detection of Multiple Metal Ions Enabled by Macroporous Graphene Foam. Anal Chem 89:11758-11764
Wang, Yu-Min; Liu, Jin-Wen; Adkins, Gary Brent et al. (2017) Enhancement of the Intrinsic Peroxidase-Like Activity of Graphitic Carbon Nitride Nanosheets by ssDNAs and Its Application for Detection of Exosomes. Anal Chem 89:12327-12333
Liu, Yang; Perez, Lizeth; Gill, Adam D et al. (2017) Site-Selective Sensing of Histone Methylation Enzyme Activity via an Arrayed Supramolecular Tandem Assay. J Am Chem Soc 139:10964-10967