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Cited by 1,224MicroRNA in disease regulationCancer-related molecular mechanisms researchCancer-related Molecular Pathways

The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells

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Johnson, Charles D., Esquela-Kerscher, Aurora, Stefani, Giovanni, Byrom, Mike, Kelnar, Kevin, Ovcharenko, Dmitriy, Wilson, Mike, Wang, Xiaowei +5 more·2007·Cancer Research
DOI 10.1158/0008-5472.can-07-1083

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Abstract

MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways. [Cancer Res 2007;67(16):7713–22]

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  • In glioblastomas, significant effects of miRNAs occur indirectly rather than by direct targeting.

    “These data are also consistent with findings in glioblastomas that significant effects of miRNAs occur indirectly rather than by direct targeting (24,43).”

    From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [43]

    The Discussion (page unavailable) says that only 25 of 176 early repressed genes were likely direct let-7 targets, and the cell-cycle section describes indirect changes downstream of direct targets. But the experiments used liver and lung cancer cell lines, not glioblastomas, so the glioblastoma-specific claim is not supported by this paper. (LLM, conf=0.85)

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Authors
Johnson, C. D., Esquela-Kerscher, A., Stefani, G., Byrom, M., Kelnar, K., Ovcharenko, D., Wilson, M., Wang, X., Shelton, J., Shingara, J., Chin, L., Brown, D., & Slack, F. J.
Affiliations
  • Asuragen (United States) (US)
  • 3Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut
  • Yale University (US)
  • 2Ambion, Inc., Austin, Texas, and
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2007-08-15
Volume
67
Issue
16
Pages
7713-7722
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-07-1083
OpenAlex
W2132194692
Cited by
1,224
References
3
Citations by year
2026: 14 · 2025: 17 · 2024: 35 · 2023: 43 · 2022: 27 · 2021: 45 · 2020: 47 · 2019: 66 · 2018: 56 · 2017: 65 · 2016: 70 · 2015: 106 · 2014: 99 · 2013: 94 · 2012: 95
FWCI
28.78
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Iris (University of Trento) (submittedVersion)
Funders
  • National Science Foundation
  • Yale University
  • National Institutes of Health (GM62594)
  • National Institute of General Medical Sciences (F32GM018663, F32GM071157, GM62594, R01GM062594)
  • National Institute of Environmental Health Sciences (F32ES012117)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
let-7 microRNA, microRNA, cell proliferation, cell cycle progression, lung cancer, tumor suppressor, A549 cells, oncogenic Ras, cell differentiation, cell cycle exit
MeSH terms
Cell Cycle, HeLa Cells, Humans, Liver Neoplasms, Lung, Genes, ras, Transfection, Gene Expression Regulation, Neoplastic, cdc25 Phosphatases, MicroRNAs, Cell Line, Tumor, Microarray Analysis, Cell Growth Processes, Cyclin-Dependent Kinase 6

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