ArticlePLoS genetics2013
Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
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- Dual Roles of miR-10a-5p and miR-10b-5p as Tumor Suppressors and Oncogenes in Diverse Cancers.International journal of molecular sciences · 2025Review
- Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions.Frontiers in genetics · 2024Article
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- Tumor-suppressive role of theiScience · 2023Article
- Comprehensive analysis of the differences between left- and right-side colorectal cancer and respective prognostic prediction.BMC gastroenterology · 2022Article
- Dissection of the microRNA Network Regulating Hedgehog Signaling inFrontiers in cell and developmental biology · 2022Article
- Recovery from heat shock requires the microRNA pathway in Caenorhabditis elegans.PLoS genetics · 2021Article
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- MicroRNA and circRNA Expression Analysis in a Zbtb1 Gene Knockout Monoclonal EL4 Cell Line.Frontiers in cellular and infection microbiology · 2021Article
- Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients.Oncotarget · 2020Article
- Sexual Dimorphism in Colon Cancer.Frontiers in oncology · 2020Review
- The role of natural killer cells in hepatocellular carcinoma development and treatment: A narrative review.Translational oncology · 2019Review
- G9a-dependent histone methylation can be induced in G1 phase of cell cycle.Scientific reports · 2019Article
- Overexpression of MicroRNA-10a in Germ Cells Causes Male Infertility by Targeting Rad51 in Mouse and Human.Frontiers in physiology · 2019Article
- The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament.Scientific reports · 2018Article
- MicroRNA-10a/b are regulators of myeloid differentiation and acute myeloid leukemia.Oncology letters · 2018Article
- Metazoan MicroRNAs.Cell · 2018Review
- MicroRNA-10a-5p suppresses cancer proliferation and division in human cervical cancer by targeting BDNF.Experimental and therapeutic medicine · 2017Article
- Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine.World journal of gastroenterology · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
miRNAs are small regulatory RNAs that, due to their considerable potential to target a wide range of mRNAs, are implicated in essentially all biological process, including cancer. miR-10a is particularly interesting considering its conserved location in the Hox cluster of developmental regulators. A role for this microRNA has been described in developmental regulation as well as for various cancers. However, previous miR-10a studies are exclusively based on transient knockdowns of this miRNA and to extensively study miR-10a loss we have generated a miR-10a knock out mouse. Here we show that, in the Apc(min) mouse model of intestinal neoplasia, female miR-10a deficient mice develop significantly more adenomas than miR-10(+/+) and male controls. We further found that Lpo is extensively upregulated in the intestinal epithelium of mice deprived of miR-10a. Using in vitro assays, we demonstrate that the primary miR-10a target KLF4 can upregulate transcription of Lpo, whereas siRNA knockdown of KLF4 reduces LPO levels in HCT-116 cells. Furthermore, Klf4 is upregulated in the intestines of miR-10a knockout mice. Lpo has previously been shown to have the capacity to oxidize estrogens into potent depurinating mutagens, creating an instable genomic environment that can cause initiation of cancer. Therefore, we postulate that Lpo upregulation in the intestinal epithelium of miR-10a deficient mice together with the predominant abundance of estrogens in female animals mainly accounts for the sex-related cancer phenotype we observed. This suggests that miR-10a could be used as a potent diagnostic marker for discovering groups of women that are at high risk of developing colorectal carcinoma, which today is one of the leading causes of cancer-related deaths.
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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.