RNA-seq analyses of human ameloblastoma and odontogenic keratocyst
Ontology highlight
ABSTRACT: Ameloblastoma (AM) is a benign but locally invasive tumor with high recurrence rates. Invasive behavior of the odontogenic tumor results in destruction of the adjacent jawbone and formation of daughter cysts, hindering the complete elimination of cancer cells during surgery. To understand the underlying mechanism of AM invasion, we compared the transcriptome of AM with that of an odontogenic keratocyst (OKC), a dental epithelium-originated cyst with non-invasive characteristics.
Project description:The aim of the study was to elucidate the cellular origin of ameloblastoma and keratocystic odontogenic tumour, neoplasms believed to arise from dental epithelial cells, by carrying out a genome-wide expression analysis.
Project description:Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumour genesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, LINC342, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAF-V600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.
Project description:During embryonic organogenesis, the odontogenic potential resides in dental mesenchyme from the bud stage until birth. Mouse dental mesenchymal cells (mDMCs) isolated from the inductive dental mesenchyme of developing molars are frequently used in the context of tooth development and regeneration. cultured mDMCs could retain the odontogenic potential for 24 h with a ratio of 60% for tooth formation, but mDMCs were incapable of supporting tooth formation after more than 24 h in culture. To reveal the underlying mechanism of the impairment of odontogenic potential, we generated gene expression profiles from mDMCs in culture using RNA-seq.
Project description:Knockdown of endogenous GDF11 downregulated the odontogenic differentiation of human dental pulp stem cells (hDPSCs). We performed RNA-seq analysis on hDPSCs transfected with GDF11 small interfering RNA (siRNA) and control siRNA after 7 days of odontogenic induction, in order to investigate the underlying mechanisms of endogenous GDF11 regulating odontogenic differentiation in hDPSC.
Project description:Using the HumanMethylation450 Beadchip, whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared.The DNA methylation profiles were obtained across approximately 485,512 CpGs in human odontogenic stem cells samples. Samples included DPSCs, DFPCs and PDLSCs from each 4 (12 in total) human individuals.
Project description:Dental pulp regeneration is significantly aided by human dental pulp stem cells (hDPSCs). An increasing number of studies have demonstrated that circular RNAs (circRNAs) are crucial in the multidirectional differentiation of many mesenchymal stem cells, but their specific functions and mechanisms remain unknown. This work aimed at elucidating the molecular mechanism by which hsa_circ_0001599 works in hDPSCs during odontogenic differentiation. The expression of hsa_circ_0001599 in hDPSCs and dental pulp tissue was determined by using quantitative real-time PCR (qRT‒PCR). The role of hsa_circ_0001599 in the odontogenic differentiation of hDPSCs and its mechanism were studied using a variety of in vivo and in vitro assessments. The odontogenic differentiation of hDPSCs was facilitated by the overexpression of hsa_circ_0001599, which activated the PI3K/AKT signalling pathway in vitro. In vivo, hsa_circ_0001599 can promote the formation of new dentin-like structures. Mechanistically, hsa_circ_0001599 enhanced ITGA2 expression by sponging miR-889-3p. Furthermore, hsa_circ_0001599 interacts with the methylation reader hnRNPA2B1, promoting hnRNPA2B1 translocation from the nucleus to the cytoplasm and increasing ITGA2 mRNA stability. This research revealed the important role of hsa_circ_0001599 in odontogenic differentiation. Thus, hDPSCs engineered with hsa_circ_0001599 have the potential to be effective therapeutic targets for dental pulp repair and regeneration
Project description:The roles of microRNAs (miRNAs) in odontogenic differentiation of human dental pulp stem cells (hDPSCs) remain largely unexplored. In this study, the underlying molecular mechanism of osteogenic differentiation in hDPSCs is investigated using miRNA profifiling.
Project description:The roles of lncRNAs and mRNAs in odontogenic differentiation of human dental pulp stem cells (hDPSCs) remain largely unexplored. In this study, the underlying molecular mechanism of osteogenic differentiation in hDPSCs is investigated using miRNA profifiling.
Project description:Human dental pulp cells have the ability to differentiate into odontoblast cells under various stimuli. The objective of our study is to investigate the efffects of glucose on gene expression of human dental pulp cells that under go odontogenic differentiation. Expression microarray were performed to identify the genes that were affected by short-term and long-term exposure to high glucose levels.