BackgroundRibosomal RNA (rRNA) is a central regulator of cell growth and may control cancer development. A cis noncoding rRNA (nc-rRNA) upstream from the 45S rRNA transcription start site has recently been implicated in control of rRNA transcription in mouse fibroblasts. We investigated whether a similar nc-rRNA might be expressed in human cancer epithelial cells, and related to any genomic characteristics.Methodology/Principal FindingsUsing quantitative rRNA measurement, we demonstrated that a nc-rRNA is transcribed in human lung epithelial and lung cancer cells, starting from approximately −1000 nucleotides upstream of the rRNA transcription start site (+1) and extending at least to +203. This nc-rRNA was significantly more abundant in the majority of lung cancer cell lines, relative to a nontransformed lung epithelial cell line. Its abundance correlated negatively with total 45S rRNA in 12 of 13 cell lines (P = 0.014). During sequence analysis from −388 to +306, we observed diverse, frequent intercopy single nucleotide polymorphisms (SNPs) in rRNA, with a frequency greater than predicted by chance at 12 sites. A SNP at +139 (U/C) in the 5′ leader sequence varied among the cell lines and correlated negatively with level of the nc-rRNA (P = 0.014). Modelling of the secondary structure of the rRNA 5′-leader sequence indicated a small increase in structural stability due to the +139 U/C SNP and a minor shift in local configuration occurrences.Conclusions/SignificanceThe results demonstrate occurrence of a sense nc-rRNA in human lung epithelial and cancer cells, and imply a role in regulation of the rRNA gene, which may be affected by a +139 SNP in the 5′ leader sequence of the primary rRNA transcript.
To address B-lineage acute lymphoblastic leukemia (B-ALL), we use a bioengineering approach to achieve high-efficient non-viral gene transfer of tumor-specific CAR+ T cells for on-demand use. Specifically, we have developed CD19-specific chimeric antigen receptors (CARs) to redirect the specificity of T cells for B-cell malignancies. We introduce CARs via a non-viral gene transfer: electroporation. We have fabricated and tested a series of high throughput micro-electroporation devices (HitMeDs) with the end result that a HitMeD can electroporate a large number (>109) human T cells within short time period (<4 hours). We connect the HitMeDs to a BTX pulse generator and a monitoring system. We have adapted HitMeDs to the electro-transfer of CAR mRNA which avoids the potential genotoxicity associated with vector integration. After electroporation, 70% to 80% of the T cells express CD19 -specific CAR.
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