ABSTRACT
The comprehensive screening of intracellular and extracellular microRNAs was performed to identify novel tumor suppressors. We found that miR-8073 was present in exosome and predominantly exported from colorectal cancer cells. Treatment with a synthetic miR-8073 mimic resulted in a dramatic decrease in the proliferation of various types of cancer cells, which was not observed in similarly treated normal cells. As little is known about the biological functions of miR-8073, its target mRNAs were analyzed by both mRNA expression and in silico sequence analyses, leading to five probable target candidates (FOXM1, MBD3, CCND1, KLK10, and CASP2) that enhance survival during the regulation of the cell cycle, cell proliferation, and apoptosis. We experimentally confirmed that miR-8073 binds the 3'-UTR of each of these mRNA target candidates and that the introduction of a synthetic miR-8073 mimic into cancer cells reduced levels of protein expression. Finally, the antiproliferative effects of miR-8073 were validated in vivo: the subcutaneous injection of a synthetic miR-8073 mimic suppressed colorectal tumor volume to 43% in tumor-bearing xenografted mice. These results suggest that because miR-8073 binds, and thus reduces the levels of, these oncogenic targets, cancer cells must actively downregulate miR-8073 as a survival mechanism. The introduction of miR-8073 into tumors could thus inhibit tumor growth, indicating its great potential for cancer therapeutics.
Subject(s)
Apoptosis/genetics , MicroRNAs/genetics , MicroRNAs/physiology , RNA, Messenger/genetics , 3' Untranslated Regions/genetics , A549 Cells , Animals , Apoptosis/physiology , Caspase 2/genetics , Cell Cycle/genetics , Cell Cycle/physiology , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Cyclin D1/genetics , Cysteine Endopeptidases/genetics , DNA-Binding Proteins/genetics , Female , Forkhead Box Protein M1/genetics , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/physiology , HCT116 Cells , HEK293 Cells , HT29 Cells , Humans , Kallikreins/genetics , MCF-7 Cells , Mice , Mice, NudeABSTRACT
The congenital absence of one or more maxillary lateral incisors poses a challenge to effective treatment planning for general dentists and dental specialists. An evaluation of anterior smile esthetics must include both static and dynamic evaluations of frontal and profile views to optimize both dental and facial appearance. This article presents a case with canine substitution treatment to replace a missing maxillary lateral incisor combined with the extraction of two mandibular lateral incisors and a small maxillary lateral incisor Both the patient's occlusion and facial appearance were significantly improved after orthodontic treatment.
Subject(s)
Anodontia/therapy , Incisor/abnormalities , Orthodontics, Corrective , Tooth Extraction , Child , Cuspid , Female , Humans , Maxilla , Orthodontic Space Closure , Tooth Movement TechniquesABSTRACT
The design of nano- and microstructures based on self-organization is a key area of research in the search for new materials, and it has a variety of potential applications in tissue engineering scaffolds. We have reported a honeycomb-patterned polymer film (honeycomb film) with highly regular pores that is formed by self-organization. This study describes the behavior of vascular endothelial cells (ECs) on honeycomb films with four different pore sizes (5, 9, 12, and 16 microm) as well as on a flat film. We examined the influence of the honeycomb pattern and pore size on cell behavior. The changes in cell morphologies, actin filaments, vinculin clusters, cell proliferation, and secreted extracellular matrix (ECM) (fibronectin, laminin, type IV collagen, and elastin) production profiles were observed by using optical, fluorescence, and scanning electron microscopy. The ECs that adhered to the flat film showed an elongated morphology with random orientation; the actin filaments and focal adhesions were not conspicuous. On the other hand, the ECs on the honeycomb films exhibited greater spreading and flattening; the degree of spreading of the ECs increased with an increase in the pore size. The actin filaments and focal adhesions appeared conspicuous, and the focal adhesions localized along the edge of the honeycomb pores were distributed over the entire projected cell area. The honeycomb film with a pore size of 5 microm showed the highest cell proliferation and ECM production profiles. These results suggest that the honeycomb film is a suitable material for designing a new vascular device.
