ArticlePloS one2012
microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 3 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Dairy Products: Is There an Impact on Promotion of Prostate Cancer? A Review of the Literature.Frontiers in nutrition · 2019Pooled it
- MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a systematic review and meta-analysis.Oncotarget · 2015Pooled it
- MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (Review).Oncology reports · 2015Pooled it
- Rephrasing the 'David-Goliath' story in the field of diabetes.Molecular biology reports · 2024Review
- MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2024Review
- Review
- miRNA in Molecular Diagnostics.Bioengineering (Basel, Switzerland) · 2022Review
- MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2022Review
- Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.The Journal of clinical investigation · 2021Article
- MicroRNAs: potential biomarkers for diagnosis and prognosis of different cancers.Translational cancer research · 2020Review
- Review
- Increased Extracellular Matrix Protein Production in Chronic Diabetic Complications: Implications of Non-Coding RNAs.Non-coding RNA · 2019Review
- Therapeutic microRNAs in human cancer.Cytotechnology · 2019Review
- Epigenetics in renal cell cancer: mechanisms and clinical applications.Nature reviews. Urology · 2018Review
- Renal Cell Carcinoma: Molecular Aspects.Indian journal of clinical biochemistry : IJCB · 2018Review
- Tyrosines-740/751 of PDGFRβ contribute to the activation of Akt/Hif1α/TGFβ nexus to drive high glucose-induced glomerular mesangial cell hypertrophy.Cellular signalling · 2018Article
- Down-regulation of microRNA-182 and microRNA-183 predicts progression of osteosarcoma.Archives of medical science : AMS · 2017Article
- PDGF receptor-β uses Akt/mTORC1 signaling node to promote high glucose-induced renal proximal tubular cell collagen I (α2) expression.American journal of physiology. Renal physiology · 2017Article
- Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved.Antioxidants & redox signaling · 2016Review
- MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by increased transcription compared to normal proximal tubular epithelial cells. Overexpression of miR-21 Sponge to quench endogenous miR-21 levels inhibited proliferation, migration and invasion of renal cancer cells. In the absence of mutation in the PTEN tumor suppressor gene, PTEN protein levels are frequently downregulated in renal cancer. We show that miR-21 targets PTEN mRNA 3'untranslated region to decrease PTEN protein expression and augments Akt phosphorylation in renal cancer cells. Downregulation of PTEN as well as overexpression of constitutively active Akt kinase prevented miR-21 Sponge-induced inhibition of renal cancer cell proliferation and migration. Moreover, we show that miR-21 Sponge inhibited the inactivating phosphorylation of the tumor suppressor protein tuberin and attenuated TORC1 activation. Finally, we demonstrate that expression of constitutively active TORC1 attenuated miR-21 Sponge-mediated suppression of proliferation and migration of renal cancer cells. Our results uncover a layer of post-transcriptional regulation of PTEN by transcriptional activation of miR-21 to force the canonical oncogenic Akt/TORC1 signaling conduit to drive renal cancer cell proliferation and invasion.
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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.