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Integrative single-cell analysis of transcriptional and epigenetic regulatory features in the human clear cell renal cell carcinoma

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is a disease with a potentially high level of tumour heterogeneity and inherited predisposition. Although many studies performed comprehensive molecular characterisation of ccRCC, the DNA regulatory mechanism is still unknown, especially at the single-cell level. Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) were performed on 19 ccRCC samples. A total of 102,723 high-quality single-cell transcriptome information, 61,693 high-quality nuclei and 190,916 unique peaks were captured. We used whole-exome sequencing to understand the heterogeneity between individuals, validate the function of long noncoding RNAs (lncRNAs) in vitro and identify protein interactions by protein mass spectrometry. Single-cell transcriptome and chromatin accessibility maps of ccRCC were constructed. We found the gene expression characteristics of different tumour cell subtypes in ccRCC and predicted their sensitivity to targeted and conventional drugs. Interestingly, we discovered that two lncRNAs (RP11-661C8.2 and CTB-164N12.1) promoted the invasion and migration of ccRCC, which were verified by in vitro experiments. Taken together, this study demonstrated the comprehensive gene expression and DNA regulation information of ccRCC and discovered and validated lncRNAs that promote tumour cell invasion and migration, which will provide new insights into the treatment of ccRCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207493 | GEO | 2023/01/08

REPOSITORIES: GEO

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