Abstract
LINE1 retrotransposons, which are thought to be the remnants of ancient integrations of retrovirus-like elements, are aberrantly (re)activated in many cancer cells. Due to LINE1-induced alterations in target gene expression and/or chromosomal rearrangements, they may be important drivers of tumorigenesis. Moreover, LINE1 encoded proteins, Open Reading Frame (ORF)1 and ORF2, may have pro-oncogenic potential through inductors of oncogenic transcription factors or inhibitors of cell cycle suppressors. The current study therefore aimed to investigate in vitro and in vivo anti-tumorigenic effects of two well-known antiretroviral drugs, zidovudine, a nucleoside analogue inhibitor of RT (NRTI), and efavirenz, a non-nucleoside RT inhibitor (NNRTI). Our data demonstrate that both drugs in clinically relevant doses significantly reduced the proliferation of murine and human cancer cell lines, as well as growth of tumors in a murine subcutaneous model. Intriguingly, we found that the combination of both zidovudine and efavirenz almost entirely blocked tumorigenesis in vivo. Because both drugs are FDA-approved agents and the combination was very well tolerated in mice, the combination therapy as presented in our paper might be an opportunity to treat colorectal tumors and metastasis to the liver in an inexpensive way.
Highlights
Endogenous Long INterspersed Elements (LINE), which belong to the superfamily of transposable genetic elements, are a major part of higher eukaryotic genomes
We focused on colorectal cancer (CRC) and hepatocellular carcinoma (HCC)
Assessment of a tissue microarrays (TMA) panel of human HCC samples, matching normal liver samples and benign tumor lesions did not demonstrate significant LINE1 staining of hepatocellular carcinoma cells (Figure S3)
Summary
Endogenous Long INterspersed Elements (LINE), which belong to the superfamily of transposable genetic elements, are a major part of higher eukaryotic genomes. LINE1 is the only active autonomous transposable element and with around 900,000 copies makes up 19.6% of the entire human DNA [1]. Their biological function is largely unknown, the tightly controlled transient expression of LINE1 is associated with early stages of germ cell and embryonic development [2]. LINE1 exerts both retrotransposition-dependent and independent functions. The former may result in alterations of target gene expression or chromosomal rearrangement, events that could have functional roles in tumorigenesis. Somatic LINE1 insertions are frequently found in colorectal cancer (CRC), less abundant in prostate and ovarian cancers, and extremely rare in multiple myeloma and glioblastoma [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
