ArticlePLoS genetics2015
Let-7 Represses Carcinogenesis and a Stem Cell Phenotype in the Intestine via Regulation of Hmga2.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
- Wdr4 regulates ribosome biogenesis and intestinal homeostasis via let-7.EMBO reports · 2026Article
- The role of HMGA1 in genome stability: Implications in human cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Milk-Derived Extracellular Vesicles and microRNAs: Potential Modulators of Intestinal Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis.The Journal of clinical investigation · 2025Article
- Decoding high mobility group A2 protein expression regulation and implications in human cancers.Discover oncology · 2024Review
- Bringing to Light the Importance of the miRNA Methylome in Colorectal Cancer Prognosis Through Electrochemical Bioplatforms.Analytical chemistry · 2024Article
- Article
- The oncogenic function of PLAGL2 is mediated via ASCL2 and IGF2 and a Wnt-independent mechanism in colorectal cancer.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- LIN28B promotes cell invasion and colorectal cancer metastasis via CLDN1 and NOTCH3.JCI insight · 2023Article
- Development and validation of an RBP gene signature for prognosis prediction in colorectal cancer based on WGCNA.Hereditas · 2023Article
- Generation and Culturing of High-Grade Serous Ovarian Cancer Patient-Derived Organoids.Journal of visualized experiments : JoVE · 2023Article
- IMP1/IGF2BP1 in human colorectal cancer extracellular vesicles.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Article
- Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation.Cell host & microbe · 2021Article
- LIN28B induces a differentiation program through CDX2 in colon cancer.JCI insight · 2021Article
- How to Use Online Tools to Generate New Hypotheses for Mammary Gland Biology Research: A Case Study for Wnt7b.Journal of mammary gland biology and neoplasia · 2020Article
- The Role of LIN28-International journal of molecular sciences · 2020Review
- High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia.International journal of molecular sciences · 2020Review
- Verbascoside inhibits progression of glioblastoma cells by promoting Let-7g-5p and down-regulating HMGA2 via Wnt/beta-catenin signalling blockade.Journal of cellular and molecular medicine · 2020Article
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Let-7 miRNAs comprise one of the largest and most highly expressed family of miRNAs among vertebrates, and is critical for promoting differentiation, regulating metabolism, inhibiting cellular proliferation, and repressing carcinogenesis in a variety of tissues. The large size of the Let-7 family of miRNAs has complicated the development of mutant animal models. Here we describe the comprehensive repression of all Let-7 miRNAs in the intestinal epithelium via low-level tissue-specific expression of the Lin28b RNA-binding protein and a conditional knockout of the MirLet7c-2/Mirlet7b locus. This ablation of Let-7 triggers the development of intestinal adenocarcinomas concomitant with reduced survival. Analysis of both mouse and human intestinal cancer specimens reveals that stem cell markers were significantly associated with loss of Let-7 miRNA expression, and that a number of Let-7 targets were elevated, including Hmga1 and Hmga2. Functional studies in 3-D enteroids revealed that Hmga2 is necessary and sufficient to mediate many characteristics of Let-7 depletion, namely accelerating cell cycle progression and enhancing a stem cell phenotype. In addition, inactivation of a single Hmga2 allele in the mouse intestine epithelium significantly represses tumorigenesis driven by Lin28b. In aggregate, we conclude that Let-7 depletion drives a stem cell phenotype and the development of intestinal cancer, primarily via Hmga2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.