عنوان

Novel Roles for miR-151a and miR-128 in Cancer

TL3ss422ws

انگلیسی

Novel Roles for miR-151a and miR-128 in Cancer

[Thesis]

Sanders, Katie

Pedersen, Irene

2016

Pedersen, Irene

2016

The discovery of microRNAs completely changed our understanding of how gene expression and regulation occurs. For 23 years, they have captivated the scientific community and revealed that though small, they are mighty and important in many basic cellular processes including growth, development, differentiation, and death. miRs are transcribed and undergo two rounds of cleavage to become ~22 nucleotide guide strands that incorporate into the RNA-induced silencing complex and finds its mRNA target to represses its expression. As a single miR can regulate multiple transcripts, they may regulate a network of targets to cause a synergistic effect. As miRs are so important, it is not surprising that they are often dysregulated during disease initiation and progression, including cancer. Cancer is one of the leading causes of death, expected to kill 595,690 people in the United States in 2016. Although diagnostics and treatments have improved, there is still much be done to combat this deadly disease. In this study, we sought to identify miRs with novel roles in cancer progression. To this end, we identified miR-151a to weaken the lung endothelial cell (EC) barrier, as well as enhance migration, invasion, sprouting and tumor-associated angiogenesis of ECs. Furthermore, we found that miR-151a is overexpressed in lung adenocarcinoma (LAC), and enhances proliferation, migration, invasion and a mesenchymal morphology in LAC cells through the direct targeting of E-cadherin, and possibly through indirect induction of Slug. In this study, we also identified a different miR as a repressor of telomerase activity, namely miR-128, through direct targeting of TERT mRNA in cancer cell lines. These studies broaden our understanding of how miRs can effect cancer progression and provide a basis for development of miR-based anti-cancer therapeutics, for which I believe there is great promise.

Gomez-Fraser, Kimberly Villanueva

Sanders, Katie

UC Irvine

p

[Thesis]

276903

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