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Updated: Jul 17, 2026
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Published on: February 21, 2018
Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression
E Oricchio1, I Sciamanna, R Beraldi
1Istituto Superiore di Sanità, Servizio BGSA, Rome, Italy.
Abstract:
Transformed cells express high levels of non-telomeric reverse-transcriptase (RT) activity of retrotransposon and endogenous retrovirus origin. We previously reported that RT inhibition, either pharmacological or through transient silencing of RT-encoding LINE-1 (L1) elements by RNA interference (RNAi), reduced proliferation, induced differentiation and reprogrammed gene expression in human tumorigenic cell lines. Moreover, the antiretroviral drug efavirenz antagonized tumor progression in animal models in vivo. To get insight into the role of retroelements in tumorigenesis, we have now produced two cell lines derived from A-375 melanoma, in which the expression of either L1 retrotransposon, or HERV-K endogenous retrovirus, was stably suppressed by RNAi. Compared to the parental A-375 cell line, cells with stably interfered L1 expression show a lower proliferation rate, a differentiated morphology and lower tumorigenicity when inoculated in nude mice. L1 silencing modulates expression of several genes and, unexpectedly, also downregulates HERV-K expression. In HERV-K interfered cells, instead, L1 expression was unaffected, and cell proliferation and differentiation remained unchanged compared to parental A-375 cells. In vivo, however, their tumorigenic potential was found to be reduced after inoculation in nude mice. These results suggest that L1 and HERV-K play specific and distinct roles in cell transformation and tumor progression.
Insights
LINE-1 (L1) retrotransposon suppression reduces melanoma cell proliferation and tumorigenicity. Human endogenous retrovirus K (HERV-K) silencing also lowers tumor potential, suggesting distinct roles for these retroelements in cancer.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Transformed cells exhibit high non-telomeric reverse-transcriptase (RT) activity from retrotransposons and endogenous retroviruses.
- Previous studies showed RT inhibition reduced proliferation and induced differentiation in human cancer cells.
- Antiretroviral drugs like efavirenz have shown potential in antagonizing tumor progression.
Purpose of the Study:
- To investigate the specific roles of LINE-1 (L1) retrotransposon and Human Endogenous Retrovirus-K (HERV-K) in tumorigenesis.
- To generate and analyze A-375 melanoma cell lines with stably suppressed L1 or HERV-K expression.
Main Methods:
- Stable RNA interference (RNAi) was used to suppress L1 retrotransposon and HERV-K expression in A-375 melanoma cells.
- Proliferation rates, cell morphology, gene expression, and tumorigenicity in nude mice were assessed.
- Comparison of L1 and HERV-K suppressed cell lines against parental A-375 cells.
Main Results:
- Stable L1 suppression led to reduced proliferation, differentiated morphology, and lower tumorigenicity in vivo.
- L1 silencing unexpectedly downregulated HERV-K expression.
- HERV-K suppression did not affect L1 expression or cell proliferation/differentiation but reduced in vivo tumorigenic potential.
Conclusions:
- LINE-1 retrotransposons and HERV-K play distinct roles in melanoma cell transformation and tumor progression.
- L1 suppression has a significant impact on both cellular characteristics and HERV-K expression.
- Targeting these retroelements may offer novel therapeutic strategies in cancer treatment.
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