ArticleCancer research2013
LIN28 Expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- MicroRNA-371-373 cluster extracellular vesicle-based communication in testicular germ cell tumors.Cell communication and signaling : CCS · 2025Article
- Replenishing co-downregulated miR-100-5p and miR-125b-5p in malignant germ cell tumors causes growth inhibition through cell cycle disruption.Molecular oncology · 2025Article
- The role of Lin28A and Lin28B in cancer beyond Let-7.FEBS letters · 2024Review
- Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy.Science advances · 2024Article
- RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within.Experimental & molecular medicine · 2024Review
- Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.British journal of cancer · 2023Article
- LncRNA CDKN2B-AS1 interacts with LIN28B to exacerbate sepsis-induced acute lung injury by inducing HIF-1α/NLRP3-mediated pyroptosis.The Kaohsiung journal of medical sciences · 2023Article
- Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.International journal of molecular sciences · 2023Review
- Article
- LIN28 Family in Testis: Control of Cell Renewal, Maturation, Fertility and Aging.International journal of molecular sciences · 2022Review
- Non-Epithelial Ovarian Cancers: How Much Do We Really Know?International journal of environmental research and public health · 2022Review
- Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs.Non-coding RNA · 2021Review
- CircPVT1 promotes proliferation of lung squamous cell carcinoma by binding to miR-30d/e.Journal of experimental & clinical cancer research : CR · 2021Article
- To Be or Not to Be a Germ Cell: The Extragonadal Germ Cell Tumor Paradigm.International journal of molecular sciences · 2021Review
- Evaluating the transcriptional fidelity of cancer models.Genome medicine · 2021Article
- Epigenetic alterations as therapeutic targets in Testicular Germ Cell Tumours : current and future application of 'epidrugs'.Epigenetics · 2021Review
- Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.Cancers · 2021Review
- Liquid Biopsies in the Clinical Management of Germ Cell Tumor Patients: State-of-the-Art and Future Directions.International journal of molecular sciences · 2021Review
- Female Germ Cell Development, Functioning and Associated Adversities under Unfavorable Circumstances.International journal of molecular sciences · 2021Review
- An update on microRNAs as potential novel therapeutic targets in testicular germ cell tumors.Intractable & rare diseases research · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Despite their clinicopathologic heterogeneity, malignant germ cell tumors (GCT) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of downregulation of the let-7 family of tumor suppressor microRNAs in malignant GCTs. Microarray results from pediatric and adult samples (n = 45) showed that LIN28, the negative regulator of let-7 biogenesis, was abundant in malignant GCTs, regardless of patient age, tumor site, or histologic subtype. Indeed, a strong negative correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, as the sequence complementary to the 2 to 7 nt common let-7 seed "GAGGUA" was enriched in the 3' untranslated regions of mRNAs upregulated in pediatric and adult malignant GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were upregulated in malignant GCT cells, confirming significant negative correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by quantitative reverse transcription PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67, and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and downregulate MYCN, AURKB, and LIN28, the latter via a double-negative feedback loop. We conclude that the LIN28/let-7 pathway has a critical pathobiologic role in malignant GCTs and therefore offers a promising target for therapeutic intervention.
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Registered trials
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