ArticleMolecular cancer2021
Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
- The identification of RNA splicing aberrations and their potential regulatory network in Chinese non-small cell lung cancer.Respiratory research · 2026Article
- Integrated Weighted Gene Co-Expression Network and Single-Cell RNA Sequencing Analyses Reveal the Prognostic Significance of Hypoxia in Gastric Cancer.Biomedicines · 2026Article
- Integrated transcriptomics and molecular docking identify hub genes and statin regulators inFrontiers in cellular and infection microbiology · 2026Article
- A noncanonical Pol III-dependent, Microprocessor-independent biogenesis pathway generates a germline-enriched miRNA family.Genes & development · 2025Article
- SGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2.Cellular and molecular life sciences : CMLS · 2025Article
- The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.Exploration (Beijing, China) · 2025Review
- Mechanical stretch-induced IGF2 overexpression in epidermal keratinocytes promotes hypertrophic scar formation through the IGF1R/p-c-Jun axis.International journal of biological sciences · 2025Article
- Copper-Based Metal-Organic Framework Nanoplatform for miRNA Delivery: Synergistic Antitumor Therapy.International journal of nanomedicine · 2025Article
- Hypoxia-induced exosomal lncRNA-PVT1 as a biomarker and mediator of EMT in hepatocellular carcinoma.Oncology research · 2025Article
- MiR-124-3p inhibits proliferation, migration, and epithelial-mesenchymal transformation in gastric cancer by targeting ITGB1.American journal of translational research · 2025Article
- Hypoxia-associated genes as predictors of outcomes in gastric cancer: a genomic approach.Frontiers in immunology · 2025Article
- Salidroside inhibited the proliferation of gastric cancer cells through up-regulating tumor suppressor miR-1343-3p and down-regulating MAP3K6/MMP24 signal molecules.Cancer biology & therapy · 2024Article
- Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway.Cancer cell international · 2024Article
- MiR-509-3p promotes gastric cancer development by activating FOXM1-mediated p38/MK2 pathway.Biomolecules & biomedicine · 2024Article
- Retracted article: MicroRNA-4521 targets hepatoma up-regulated protein (HURP) to inhibit the malignant progression of breast cancer.Bioengineered · 2024Article
- Circ_0001361/miR-490-5p/IGF2 Axis Regulates the Viability and Apoptosis of Neuroblastoma Cells.Neurochemical research · 2024Article
- Article
- miR-4521-A novel biomarker for human lentigos.Experimental dermatology · 2024Article
- HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression.Cancer medicine · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC.
methodsThe microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model.
resultsIn this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo.
conclusionsOur results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.
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