Modulation of K-ras-dependent lung tumorigenesis by microRNA-21

By M. Hatley, D. Patrick, Matthew R. Garcia, J. Richardson, R. Bassel-Duby, Eva van Rooij, E. Olson. Cancer Cell, 2010

651 citations recorded by the source corpus.

SUMMARY Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) accounts for 80% of cases. MicroRNA-21 (miR-21) expression is increased and predicts poor survival in NSCLC. Although miR-21 function has been studied in vitro using cancer cell lines, the role of miR-21 in tumor development in vivo is unknown. We utilize transgenic mice with loss-of-function and gain-of-function miR-21 alleles combined with a model of NSCLC to determine the role of miR-21 in lung cancer. We show that over-expression of miR-21 enhances tumorigenesis and genetic deletion of miR-21 partially protects against tumor formation. MiR-21 drives tumorigenesis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ea1aaa83b1883a1290ce31db3401b12568b668c7

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Citations in the corpus

microRNAs in cancer (2013, background): “Genetic deletion of miR-21 reduced lung tumor burden following activation of a mutant KrasG12D allele, and correspondingly, a miR-21 transgene increased tumor outgrowth (78).”
MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer (2015, background): “These include germline transgenic or knockout mice for the following: miR-155, which, if overexpressed in B cell lineage, induces B cell malignancy [113]; miR-21, which leads to lung tumorigenesis if ubiquitously deleted [114]; miR-17-92 and its paralogs, whose overexpression in lymphocytes induces ”
The Lin28/let-7 axis regulates glucose metabolism (2011, background): “…(Figure 6E), a concept that is consistent with the hypotheses that miRNAs and RNA binding proteins regulate signaling pathways by tuning the production of a broad array of proteins rather than switching single components on or off (Kennell et al., 2008; Hatley et al., 2010; Small and Olson, 2011).”
MicroRNA and cancer (2012, background): “Studies in miR-21 knockout mice have demonstrated reduced lung tumour burden following activation of a mutant KrasG12D allele and, in accordance, a miR-21 transgene resulted in increased tumour outgrowth (Hatley et al., 2010).”
MicroRNAs in human cancer. (2013, background): “Examples include the TP53 regulated mir-34a [57, 58], the RAS regulated mir-21 [33, 59, 60] and the MYC regulated mir-17-92 gene cluster [61, 62].”
microRNA as Biomarkers and Diagnostics (2016, background): “The oncomir, miR-21, targets PTEN (Meng et al., 2007) and SPRY2 (Sayed et al., 2008), promoting invasion and migration, as well as tumorigenesis by inhibiting the negative regulators of the Ras/MEK/ERK pathway (Hatley et al., 2010).”
Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling (2011, background): “We noted the drastic up-regulation of miR-21 in carcinomas, recently identified as an oncogene in mouse models (45, 46).”
MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, neutral): “, three groups generated mir-21 -knockout or mir-21 -overexpressing mic”
MicroRNAs in stress signaling and human disease (2012, background): “Other miRNAs that appear to participate in similar positive feedback pathways to stably enforce oncogenic signaling programs include miR-21, which is activated by MAPK/ERK signaling and represses negative regulators of this signaling cascade (Hatley et al., 2010), and the miR-143/145 cluster, which ”