This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dicer is a highly conserved RNase III type enzyme found in almost all eukaryotes that is essential for the RNA interference (RNAi) and microRNA pathways. During the last several years an increasing number of reports have found Dicer to be aberrantly expressed in different types of cancer, including oral squamous cell carcinomas (OSCCs). Recently, the dicer gene has been predicted to produce 11 mRNA splice variants bearing modified coding sequences. Our preliminary data suggests that one of these predicted Dicer mRNA splice variants is expressed in cells and appears to be upregulated in OSCC cell lines. Because the expression and function of the Dicer mRNA splice variants have not been well characterized and it currently remains unclear as to their biological significance, this proposal will explore the role of this particular Dicer mRNA splice variant in relation to oral cancer biology. Therefore, to better assess and correlate the expression patterns of the Dicer mRNA splice variant relative to OSCCs and disease progression this proposal will characterize its mRNA and protein expression levels in both OSCC cell lines and tissues ranging from dysplastic to invasive OSCCs in relation to non-cancerous counterparts. Furthermore, to enhance our understanding of the mechanisms regulating its aberrant expression this study will also analyze whether its aberrant expression in oral cancer cells is due to transcriptional and/or post-transcriptional regulatory mechanisms. Because the significance of the dysregulation of this splice variant in terms of cancer cell properties is not understood, this proposal will further seek to examine the biological effects of reducing the levels of the Dicer mRNA splice variant in oral cancer cells using RNAi knockdown strategies and analyze the effects of overexpressing it in both primary and immortalized human oral keratinocytes. The biological metrics will include cell proliferation, apoptosis, cell migration and invasion, and oncogenic transformation assays. By successfully addressing these specific aims this will lead to a better understanding of oral cancer biology. Furthermore, it will shed new insights into the function of Dicer mRNA splice variants and what roles they play in oral cancer development and progression.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017696-10
Application #
8360488
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-06-01
Project End
2012-09-04
Budget Start
2011-06-01
Budget End
2013-05-31
Support Year
10
Fiscal Year
2011
Total Cost
$175,831
Indirect Cost
Name
Medical University of South Carolina
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Heise, Tilman; Kota, Venkatesh; Brock, Alexander et al. (2016) The La protein counteracts cisplatin-induced cell death by stimulating protein synthesis of anti-apoptotic factor Bcl2. Oncotarget 7:29664-76
Sabatini, Camila; Mennito, Anthony S; Wolf, Bethany J et al. (2015) Incorporation of bactericidal poly-acrylic acid modified copper iodide particles into adhesive resins. J Dent 43:546-55
Wood, James S; Marlow, Nicole M; Cayouette, Monica J (2015) Accuracy of dental torque wrenches. Gen Dent 63:e20-2
Hunt, Kelly J; Kistner-Griffin, Emily; Spruill, Ida et al. (2014) Cardiovascular risk in Gullah African Americans with high familial risk of type 2 diabetes mellitus: project SuGAR. South Med J 107:607-14
Cooley, Marion A; Harikrishnan, Keerthi; Oppel, James A et al. (2014) Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. Bone 69:30-8
Cantini, Liliana P; Andino, Lourdes M; Attaway, Christopher C et al. (2014) Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells. Mol Cancer 13:190
Shi, Changcheng; Cisewski, Sarah E; Bell, P Darwin et al. (2014) Measurement of three-dimensional anisotropic diffusion by multiphoton fluorescence recovery after photobleaching. Ann Biomed Eng 42:555-65
Qin, Tingting; Matmati, Nabil; Tsoi, Lam C et al. (2014) Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network. Nucleic Acids Res 42:e138
Yuen, H K; Hant, F N; Hatfield, C et al. (2014) Factors associated with oral hygiene practices among adults with systemic sclerosis. Int J Dent Hyg 12:180-6
Miller Jr, Preston D; McEntire, Mark L; Marlow, Nicole M et al. (2014) An evidenced-based scoring index to determine the periodontal prognosis on molars. J Periodontol 85:214-25

Showing the most recent 10 out of 134 publications