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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Related Experiment Video

Updated: Mar 28, 2026

Analysis of LINE-1 Retrotransposition at the Single Nucleus Level
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The oncogenic microRNA miR-222 promotes human LINE-1 retrotransposition.

Tomer Friehmann1, Yamama Abu Mohsen1, Yehuda Schlesinger1

  • 1The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah University Medical Center (Hadassah Hebrew University Hospital), Jerusalem, Israel.

RNA Biology
|May 27, 2025
PubMed
Summary

MicroRNA-222 (miR-222) promotes Long Interspersed Element-1 (LINE-1) retrotransposition in hepatocellular carcinoma (HCC). This oncogenic microRNA reduces let-7c expression, contributing to LINE-1 activation in HCC cells.

Keywords:
HCClet-7miR-222microRNAretrotransposon

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RNA Next-Generation Sequencing and a Bioinformatics Pipeline to Identify Expressed LINE-1s at the Locus-Specific Level
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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Long Interspersed Element-1 (LINE-1) retrotransposition is implicated in cancer development and tumor heterogeneity, particularly in hepatocellular carcinoma (HCC).
  • While proteins and some microRNAs (miRs) are known regulators of LINE-1 activity, the specific roles of certain miRs in HCC remain under investigation.

Purpose of the Study:

  • To investigate the role of the oncogenic miR-222 in regulating LINE-1 retrotransposition (RTP) in hepatocellular carcinoma (HCC).
  • To elucidate the mechanisms by which miR-222 influences LINE-1 RTP in HCC cell lines.

Main Methods:

  • Generation of miR-222-knockout HCC cell lines (Huh7 and FLC4).
  • RNA-sequencing (RNA-seq) analysis of miR-222-knockout Huh7 cells.
  • Global proteomics analysis of miR-222-knockout Huh7 and FLC4 cells.
  • Assessment of miR-222-3p and miR-222-5p activity on LINE-1 RTP.

Main Results:

  • miR-222 was confirmed to promote LINE-1 RTP in human HCC and other cell lines in vitro.
  • Both miR-222-3p and miR-222-5p demonstrated cell-type specific activation of LINE-1 RTP.
  • miR-222 was found to decrease let-7c expression in both HCC cell lines.
  • The reduction in let-7c expression by miR-222 contributes to the promotion of LINE-1 RTP in Huh7 cells.

Conclusions:

  • miR-222 is an oncogenic regulator that enhances LINE-1 retrotransposition in hepatocellular carcinoma.
  • The mechanism involves miR-222-mediated downregulation of let-7c, leading to increased LINE-1 activity.
  • These findings highlight a novel regulatory pathway involving microRNAs in the context of LINE-1 activity in cancer.