Hypoxia-induced miR-424 decreases tumor sensitivity to chemotherapy by inhibiting apoptosis.
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TLDR
It is found that hypoxia induces miR-424 expression and that miR -424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3′ untranslated region.Abstract:
Chemotherapy resistance of tumor cells is a big challenge. Adaption to hypoxia is an essential cellular response that is controlled by the master oxygen-sensitive transcription factor HIF1 (hypoxia-inducible factor 1). The mechanism by which tumor cells acquire resistance to chemotherapy under hypoxic conditions is not fully understood. In this study, we found that hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3′ untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 enhanced apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples. These results suggest that miR-424 is a potential molecular target for tumor therapy.read more
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Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression.
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TL;DR: The study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer- derived exosomes, which modulates tumour vasculature.
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MicroRNAs in Pulmonary Arterial Hypertension
TL;DR: The current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts are reviewed and emerging trends are identified.
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MicroRNA-421 regulated by HIF-1α promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer.
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TL;DR: Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer in vivo and in vitro and E-cadherin and caspase-3 were identified as targets.
References
More filters
Journal ArticleDOI
Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets
TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.
Journal Article
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Journal ArticleDOI
Oncomirs — microRNAs with a role in cancer
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
Journal ArticleDOI
The impact of microRNAs on protein output
TL;DR: The impact of micro RNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.
Journal ArticleDOI
Widespread changes in protein synthesis induced by microRNAs
Matthias Selbach,Björn Schwanhäusser,Nadine Thierfelder,Zhuo Fang,Raya Khanin,Nikolaus Rajewsky +5 more
TL;DR: It is shown that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild, and the data suggest that a mi RNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.