ArticleOncogene2015
Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.
- Prognostic Value of CD63 Expression in Solid Tumors: A Meta-analysis of the Literature.In vivo (Athens, Greece)Pooled it
- Exosomal miRNAs: Key Regulators of the Tumor Microenvironment and Cancer Stem Cells.International journal of molecular sciences · 2025Review
- Biogenesis and functional implications of extracellular vesicles in cancer metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- FGFRL1: Structure, Molecular Function, and Involvement in Human Disease.Current issues in molecular biology · 2025Review
- A Robust NSCLC Biomarker- miR-7-5p: ItsMicroRNA (Shariqah, United Arab Emirates) · 2025Article
- Exosomes in arteriovenous fistula stenosis.Frontiers in cell and developmental biology · 2025Review
- The Role of Exosomes as a Key Factor of Cytostatic Resistance in Cancer: Mechanisms of Action, Potential Biomarkers, and Possible Exosome-Based Therapies.Oncology research · 2025Review
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Harnessing exosomes as cancer biomarkers in clinical oncology.Cancer cell international · 2024Review
- Review
- TIMP-1 Promotes Expression of MCP-1 and Macrophage Migration by Inducing Fli-1 in Experimental Liver Fibrosis.Journal of clinical and translational hepatology · 2024Article
- RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.Brain and behavior · 2024Article
- Timp1 Deletion Induces Anxiety-like Behavior in Mice.Neuroscience bulletin · 2024Article
- Decoding the Versatile Landscape of Autophagic Protein VMP1 in Cancer: A Comprehensive Review across Tissue Types and Regulatory Mechanisms.International journal of molecular sciences · 2024Review
- RNAkines are secreted messengers shaping health and disease.Trends in endocrinology and metabolism: TEM · 2024Review
- VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology.Frontiers in cell and developmental biology · 2024Review
- Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.Frontiers in cell and developmental biology · 2024Review
- MiR-1246b, a novel miRNA molecule of extracellular vesicles in bronchoalveolar lavage fluid, promotes nodule growth through FGF14 in patients with lung cancer.Cell death & disease · 2023Article
- The therapeutic potential of exosomes in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Exosomal non-coding RNAs in angiogenesis: Functions, mechanisms and potential clinical applications.Heliyon · 2023Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of metalloproteinases-1 (TIMP-1) recently emerged as a pro-metastatic factor highly associated with poor prognosis in a number of cancers. This correlation seemed paradox as TIMP-1 is best described as an inhibitor of pro-tumourigenic matrix metalloproteinases. Only recently, TIMP-1 has been revealed as a signalling molecule that can regulate cancer progression independent of its inhibitory properties. In the present study, we demonstrate that an increase of both exogenous and endogenous TIMP-1 led to the upregulation of miR-210 in a CD63/PI3K/AKT/HIF-1-dependent pathway in lung adenocarcinoma cells. TIMP-1 induced P110/P85 PI3K-signalling and AKT phosphorylation. It also led to increase of HIF-1α protein levels positively correlating with HIF-1-regulated mRNA expression and upregulation of the microRNA miR-210. Downstream targets of miR-210, namely FGFRL1, E2F3, VMP-1, RAD52 and SDHD, were decreased in the presence of TIMP-1. Upon the overexpression of TIMP-1 in tumour cells, miR-210 was accumulated in exosomes in vitro and in vivo. These exosomes promoted tube formation activity in human umbilical vein endothelial cell (HUVECs), which was reflected in increased angiogenesis in A549L-derived tumour xenografts. Activation and elevation of PI3K, AKT, HIF-1A and miR-210 in tumours additionally confirmed our in vitro data. This new pro-tumourigenic signalling function of TIMP-1 may explain why elevated TIMP-1 levels in lung cancer patients are highly correlated with poor prognosis.
Indexed as
Identifiers
What OpenQuestion holds
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.