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Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations & Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations & Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …

Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt

Wayne State University Dissertations

The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …