Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Stevon C. Taylor - Jackson State University
Co-Author(s): Maricica Pacurari, Jackson State University, Jackson, MS
MicroRNAs are short strands of RNAs that regulate gene expression, thus mediating pathogenesis of human diseases, including lung cancer. MicroRNA-1 has been shown to regulate cell proliferation, migration, and apoptosis. Moreover, several studies suggest that microRNA-1 may indeed function as a tumor suppressor microRNA. Using bioinformatics tools, we identified a novel microRNA-1 target thrombospondin 1 (THBS1). THBS1, a matricellular protein, which regulates multiple cellular processes involved in tissue repair, remodeling and particularly regulating cell adhesion, migration and proliferation. In the present study, we investigated whether carbon nanofiber regulate miRNA-1 and its target THBS1 in human adenocarcinoma cells. Using alveolar epithelial type II cells (A549), the regulation of miRNA-1 by carbon nanofiber and its target THBS1 were analyzed using real-time quantitative PCR (qPCR) and western blot. SnoU47 was used as endogenous control miRNA. A549 cells were exposed to multi-wall carbon nanotubes (MWCNT) (20 μg/ml) for 6 or 24 h. Total RNA was extracted using the trizol method. MicroRNA-1 cDNA was generated followed by real-time miRNA-1 qPCR analysis. MWCNT differentially regulated the expression of miR-1 and its target THBS-1 in A549 cells. Inhibition of miRNA-1 expression affected cell morphology by inducing cell rounding and cell death, whereas overexpression of miRNA-1 had no effect on cell morphology. These results suggest that MWCNT subsequently involved in the regulation of microRNA-1, as well as THBS-1 in alveolar lung epithelial cells. THBS-1 regulates TGF-beta signaling, thus positively influencing wound healing and fibrosis. These results indicated a possible mechanism for MWCNT pathological effect on lung tissue including lung fibrosis. The proposed mechanism is via microRNA-1/THBS-1/TGFbeta fibroproliferative axis.
Not SubmittedFunder Acknowledgement(s): This research is supported by Career development pilot grant to Dr. Pacurair through the NIH/NCRR-RCMI Center for Environmental Health at Jackson State University (JSU) (Grant No. G12MD007581).
Faculty Advisor: Maricica Pacurari, Maricica.pacurari@jsums.edu