Publications by authors named "P Mita"
LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint.
Proc Natl Acad Sci U S A
February 2022
Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress.
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- LINE-1 is an autonomous retroelement that has accumulated about 500,000 sequences in the human genome, with only 80-100 capable of mobilization, primarily in cancer cells.
- The study optimized CRISPR Cas9 guide RNAs to specifically target the L1Hs promoter, identifying three gRNAs that effectively distinguish L1Hs from older LINE-1 sequences.
- Using the C-BERST method, researchers discovered both known and new LINE-1 transcriptional regulators, including the novel discovery of DUSP1 as a regulator of LINE-1 transcription in cancer.
Article Synopsis
- Transposable elements, or transposons, are repetitive DNA sequences that can move within genomes, often increasing their copy numbers significantly.
- This Review explores how retrotransposons, a major type of transposon, may impact the aging process and contribute to age-related diseases in complex organisms like humans.
- Recent findings shed light on the role of retrotransposons in somatic tissues throughout an individual's life, revealing their interactions with human health and biological functions beyond just germline activity.
Article Synopsis
- LINE-1 is a retroelement that can insert copies of itself into the genome and is typically repressed in healthy cells, but its expression is found in nearly 50% of tumors, particularly prostate cancer.
- Research identified that in androgen-independent prostate cancer cells, there are increased levels of LINE-1 RNA and different expression patterns compared to androgen-dependent cells.
- The study also revealed that ORF1p, a LINE-1 protein, binds not only to LINE-1 RNA but also to various non-LINE-1 mRNAs, which may be relevant to the biology of prostate cancer as seen in tumor data from The Cancer Genome Atlas.