The Mechanistic Studies Of MicroRNA And Growth Hormone In Tumor Progression In Vivo

First Part:Breast cancer is one of the most common cancer world-widely. In recent years, its incidence is also increasing rapidly in China, posing great threat to the patient and their family and also increasing social financial burden. To cure this disease, we have to elucidate both the mechanism of its initiation and development in our system. MicroRNAs are endogenous small non-coding RNAs composed of21-24nucleotides. They bind to target the3’UTR of the target mRNAs by the seed regions at its5’end, thus leading to the repression of translation of target genes. Li,GP et al had validated that miR-1254has a critical role as the suppressor in breast cancer. Here we validated that miR-1254exerted tumor suppressive roles in vivo, and verified that miR-1254can also regulate the expression of target genes in vivo.Second Part:Colon cancer as cancer develops in the colon or rectum exhibits a high incidence in the world. Wang,JJ et al found that hGH exerted an important role in colon cancer. She had validated that hGH can promote the proliferation, metastasis of colon cancer cells and promotes its cancer stem cell traits. Here, to explore the function of hGH in vivo, we conducted a series of experiments and verified that hGH can promote the growth and decrease cell apoptosis, increase colon the self-renewal of cancer stem cells in colon cancer cells. Surprisingly, we also found that hGH can inhibit DLD-1cell’s migration to the lung, which contradicts its pro-invasion roles in vitro.Third Part:The GH-IGF-IGFBP axis exerted a pivotal role in the oncogenesis and progression of a number types of cancers. We aim to inhibit GH-IGF1signal transduction pathway in vivo to examine its implication on tumor progression.In this thesis, we had induced the expression of endogenous hGH specific antibody in rat and mouse, and identified the relative activity of GH-IGF1signal pathway in several mouse cancer cell lines. We also tried to optimize the cellular model system needed for testing the roles of GH-IGF1signaling pathways in cancer progression.