ArticleCell death & disease2017
miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 103 citations in OpenAlex.
- Article
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- Stage-Specific miRNA Profiling Reveals Key Regulators of EMT and EGFR-TKI Resistance in Gallbladder Cancer.Cancers · 2026Article
- B cell extracellular vesicles influence melanoma response to immune checkpoint therapy.Science advances · 2025Article
- SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer.Journal of translational medicine · 2025Article
- The potential of the South African plant Tulbaghia Violacea Harv for the treatment of triple negative breast cancer.Scientific reports · 2025Article
- Review
- Integrated analysis and experimental validation of E2F2 as a potential prognostic biomarker and its oncogenic roles in serous ovarian cancer.Frontiers in molecular biosciences · 2025Article
- Mesenchymal Stem Cell-Exosomal miR-99a Attenuate Silica-Induced Lung Fibrosis by Inhibiting Pulmonary Fibroblast Transdifferentiation.International journal of molecular sciences · 2024Article
- Characterization of the stem cell landscape and identification of a stemness-associated prognostic signature in bladder cancer.Cancer cell international · 2024Article
- The crosstalk between non-coding RNAs and cell-cycle events: A new frontier in cancer therapy.Molecular therapy. Oncology · 2024Review
- The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms.Nature communications · 2024Article
- The role of E2F2 in cancer progression and its value as a therapeutic target.Frontiers in immunology · 2024Review
- MiR-99a-5p up-regulates LDLR and functionally enhances LDL-C uptake via suppressing PCSK9 expression in human hepatocytes.Frontiers in genetics · 2024Article
- MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes.Cancers · 2023Article
- The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer.International journal of molecular sciences · 2023Review
- Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies.Cancers · 2022Review
- Circ-CUL2/microRNA-888-5p/RB1CC1 axis participates in cisplatin resistance in NSCLC via repressing cell advancement.Bioengineered · 2022Article
- MiR-223 Promotes Tumor Progression via Targeting RhoB in Gastric Cancer.Journal of oncology · 2022Article
- circPTN Promotes the Progression of Non-Small Cell Lung Cancer through Upregulation of E2F2 by Sponging miR-432-5p.International journal of genomics · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is one of the most aggressive tumours with very low life expectancy. Altered microRNA expression is found in human tumours because it is involved in tumour growth, progression and metastasis. In this study, we analysed microRNA expression in 47 lung cancer biopsies. Among the most downregulated microRNAs we focussed on the miR-99a characterisation. In vitro experiments showed that miR-99a expression decreases the proliferation of H1650, H1975 and H1299 lung cancer cells causing cell cycle arrest and apoptosis. We identified two novel proteins, E2F2 (E2F transcription factor 2) and EMR2 (EGF-like module-containing, mucin-like, hormone receptor-like 2), downregulated by miR-99a by its direct binding to their 3'-UTR. Moreover, miR-99a expression prevented cancer cell epithelial-to-mesenchymal transition (EMT) and repressed the tumourigenic potential of the cancer stem cell (CSC) population in both these cell lines and mice tumours originated from H1975 cells. The expression of E2F2 and EMR2 at protein level was studied in 119 lung cancer biopsies. E2F2 and EMR2 are preferentially expressed in adenocarcinomas subtypes versus other tumour types (squamous and others). Interestingly, the expression of E2F2 correlates with the presence of vimentin and both E2F2 and EMR2 correlate with the presence of β-catenin. Moreover, miR-99a expression correlates inversely with E2F2 and directly with β-catenin expression in lung cancer biopsies. In conclusion, miR-99a reveals two novel targets E2F2 and EMR2 that play a key role in lung tumourigenesis. By inhibiting E2F2 and EMR2, miR-99a represses in vivo the transition of epithelial cells through an EMT process concomitantly with the inhibition of stemness features and consequently decreasing the CSC population.
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