Molecular structure study of miro-RNA associated with race in human uterine leiomyomas

B97 Control of gene expression can occur at any event ranging from promotion of transcription to stabilization of the mature polypeptide product. One of the major functions on miRNA appears to be gene regulation. It is a single-stranded RNA molecule of about 21-23 nucleotides in length thought to regulate the expression of other genes involved in cellular function such as apoptosis or cell proliferation. For that purpose, a miRNA is complementary to a part of one or more mRNAs. miRNAs can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. ULM are fibroid tumors that are noncancerous growths in the uterus. Frequently found in women between the ages 30-45, fibroids are the most common type of abnormal pelvic growth in women. They account for about one quarter of all hysterectomies performed in the United States each year. Many genes are dysregulated in ULMs due to abnormal expression of miRNAs. Genetic epidemiological studies have illustrated a higher incidence of ULMs in first degree family members than in the general population. Familial aggregation and twin studies support the heritability of these tumors. A higher rate in monozygotic twins than heterozygotic twins, and a higher incidence in the disease in black women than in white women. Ethnic predisposition studies show LM is more frequent in women of African origin than women of other ethnic groups. In a study of 206 miRNAs, 45 were significantly up or down regulated in ULMs. The top five genes dysregulated in that study were the let-7 family, miR-21, miR29b, miR-197 and miR-23b. We examined these molecules involved in cancer and immune response by empirical and molecular dynamic calculations. We also examined miRNAs that were selected from different cancer types and involvement in human immune response. We began the project by examining the folding of mRNA by RNAstructure version 4.3. These sequences were downloaded from the Sanger miRNA database and prepared by using the RNAshuffle, RNAgather, HyperChem and Excel for mathematical analysis. Significance analysis revealed that subsets of miRNA were strongly associated with tumor size and race. The free energy of folding for the set of miRNAs examined partitions the miRNAs into two classes, those with or without secondary structure. We then compared the folding energies to those calculated from sequences that were randomized and computed z-scores. The results indicate that let-7 family, miR-21, miR29b, miR-197 and miR-23b avoid secondary structure which may assist in hybridization to target mRNAs. In comparison, we examined the folding of miRNA by normal tissues and cancers such as: miRNA-18, miRNA124A and miRNA-100. Using similar methods as stated above. These results suggest the sequences of miRNA avoid self-structures that may slow hybridization to target mRNAs. These secondary structure values can be used to classify the miRNAs and to uncover correlations to functional categories such as disease outcome or expression levels in tissues. Conformational free energies are available for correlational analysis to clinical or biochemical parameters. This work was supported by NIH1NIGMS/MBRS/SCORE/RISE (grant # S06GM08247).