Abstract
Colon tumor growth is significantly reduced or ablated using a new microRNA inhibitor system
The FASEB journal, Vol.33(S1), pp.250.7-250.7
04/2019
DOI: 10.1096/fasebj.2019.33.1_supplement.250.7
Abstract
MicroRNAs (miRs) are biomarkers of cancer development and progression, they regulate cell fate, stemness and embryonic development. It is well‐known that miRs play a role in cancer and are associated with numerous types of cancer as either oncogenes or tumor‐suppressor genes. Colorectal cancer is associated with increased levels of miR‐210, and as miR‐210 levels increase life expectancy decreases. We developed a new miR therapeutic termed the Plasmid‐based microRNA Inhibitor System (PMIS). The PMIS is very stable, efficient, has high specificity (no off‐target effects) and affinity for specific miRs and is not toxic to cells or animals. We made PMIS‐miR‐210 and PMIS‐vector only stably transduced human SW620 colon cancer cell lines to determine the effect of inhibiting miR‐210 on cell growth and phenotypes. The PMIS‐miR‐210 cells proliferated very slowly (25% of the rate of PMIS‐vector only cells). RNA‐sequencing experiments and bioinformatics analyses revealed several new genes targeted by miR‐210 and new pathways in colon tumor progression. We have identified a miR regulatory loop controlling the expression of other miRs. Nude mice were injected with PMIS‐miR‐210 or PMIS‐vector stably expressing human colon cancer cells and 5 out of 8 mice with colon cancer cells expressing PMIS‐miR‐210 did not form tumors compared to the controls (PMIS‐vector, 8 of 8 had tumors). To demonstrate the effectiveness of PMIS‐miR‐210 as a therapeutic agent, nude and NSG mice were injected with colon cancer cells (BLI imaging) and tumors were allowed to form (3 weeks), mice were then injected with “naked” plasmid DNA PMIS‐miR‐210 or vector control into and surrounding the solid tumor mass at several concentrations. No or small tumors were observed in 16 of the 16 mice injected with PMIS‐miR‐210 compared to controls after 2 weeks of further growth (PMIS‐vector, 10 of 10 had no effect on tumor growth). Capecitabine oral administration was used to compared tumor growth to the PMIS‐miR‐210 group and was significantly less effective than the PMIS therapeutic treatment. Unlike other microRNA inhibitors we prove that direct injection of a naked plasmid DNA expressing the PMIS‐miR‐210 inhibitor reduced or completely inhibited tumor growth, without using toxic delivery systems. The PMIS has great potential as a new therapeutic biological drug for cancer treatments.
Support or Funding Information
NIH grants R43DE027569, R03EB025873 and R01DE026433 to BAA and LH
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Colon tumor growth is significantly reduced or ablated using a new microRNA inhibitor system
- Creators
- Brad Amendt - University of IowaSteven Eliason - University of IowaLiu Hong - University of IowaHuojun Cao - University of IowaFenghuang Zhan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.33(S1), pp.250.7-250.7
- DOI
- 10.1096/fasebj.2019.33.1_supplement.250.7
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- The Federation of American Societies for Experimental Biology
- Number of pages
- 1
- Grant note
- NIH (R43DE027569; R03EB025873; R01DE026433)
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Endodontics; Prosthodontics; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984288751102771
Metrics
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