The Promotion Of Somatic Cell Reprogramming By MicroRNA-302-367 Cluster And The Inhibition Of Lung Cancer Cell Proliferation By MicroRNA-145

micoRNAs are 19-23nt single-stranded small RNAs ,which regulate gene expression by binding to 3'-UTR of mRNA to inhibit its translation or/and induce its degradation. miRNAs play critical roles in a plethora of biological processes including cell apoptosis, cell proliferation, differentiation, cell metabolism, tumorgenesis and so on. To understand the roles of miRNA in these processes is important to cell biology research.Many miRNAs found as clusters in genome are always co-transcribed, and then processed into mature miRNAs to regulate gene expression. These clustered miRNAs are sometimes functionally related. Several miRNA clusters highly expressed in embryonic stem cells and induced pluripotent stem cells are studyed on their roles in somatic cell reprogramming. We found that miR-106a-363 cluster and miR-302-367 cluster can significantly increase somatic cell reprogramming. Futhermore, we found that the expression of some members of miR-106a-363 is regulated by c-Myc. And miR-302-367 cluster in 4 transcription factors showed higher expression than that in 3 transcription factors, which indicated that the expression of miR-302-367 may require the opening of chromatin structure. Further study showed that miR-302 inhibits the expression of tgfbr2 by targeting its 3'-UTR, promoting somatic cell reprogramming at least partially through the Mesenchynal Epithelial Transition (MET). In human systems, we also found that miR-302-367 cluster can increase the efficiency of somatic reprogramming.In lung cancer study, we found that miR-145 significantly inhibits the proliferation of lung cancer cells and causes the cell cycle arrest in G1 phase, while don't affect cell apoptosis. Further study showed that miR-145 directly target on CDK6 through binding to its 3'-UTR. siRNA targeting CDK6 showed similar effects on lung cancer cells as miR-145. In mouse exnograft models, miR-145 mimics can also inhibit tumor growth, these indicate that miR-145 might be a potential drug candidate for lung cancer therapy in the future.