ArticleMolecular carcinogenesis2016
Down-regulation of microRNA-9 leads to activation of IL-6/Jak/STAT3 pathway through directly targeting IL-6 in HeLa cell.
Article in Molecular carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- MicroRNA Dysregulation in HPV-Driven Cervical Cancer: A Review of Oncoprotein-Targeted Signaling Pathways.Life (Basel, Switzerland) · 2026Review
- N-glycosylation of GSTO1 promotes cervical cancer migration and invasion through JAK/STAT3 pathway activation.Functional & integrative genomics · 2025Article
- Role of HPV E7/miR-143-3p/SH2D3A pathway in regulating the occurrence and development of cervical cancer.Journal of gynecologic oncology · 2025Article
- Assessing the Biological Markers of MiRNA-9 and 192 Expression Levels in Cervical Cancer.Advanced biomedical research · 2025Article
- Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.Frontiers in immunology · 2025Article
- Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT.Pediatric nephrology (Berlin, Germany) · 2024Article
- Article
- Review
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- The regulatory relationship between transcription factor STAT3 and noncoding RNA.Cellular & molecular biology letters · 2024Review
- Understanding the role of miRNAs in cervical cancer pathogenesis and therapeutic responses.Frontiers in cell and developmental biology · 2024Review
- Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.Journal of neurotrauma · 2023Review
- Tackling cellular senescence by targeting miRNAs.Biogerontology · 2022Review
- Hsa_circ_0017728 as an oncogene in gastric cancer by sponging miR-149 and modulating the IL-6/STAT3 pathway.Archives of medical science : AMS · 2022Article
- Circulating microRNA 9-3p and serum endocan as potential biomarkers for hepatitis C virus-related hepatocellular carcinoma.World journal of hepatology · 2021Article
- MicroRNA-9 as a paradoxical but critical regulator of cancer metastasis: Implications in personalized medicine.Genes & diseases · 2021Review
- TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia.Communications biology · 2021Article
- Implications of microRNA 21 and its involvement in the treatment of different type of arthritis.Molecular and cellular biochemistry · 2021Review
- Noncoding RNAs: the shot callers in tumor immune escape.Signal transduction and targeted therapy · 2020Review
- miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis.Journal of applied oral science : revista FOB · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNA-9 (miR-9) presents to exert distinct and even opposite functions in different kinds of tumors through targeting different cellular genes. However, its role in cervical adenocarcinoma remains uncertain. Here, we report that miR-9 is down-regulated in cervical adenocarcinoma due to its frequent promoter-hypermethylation and exerts its tumor suppressor role through inhibiting several novel target genes, including interleukin-6 (IL-6). The promoters of miR-9 precursors (mir-9-1, -2, and -3) were hypermethylated in cervical adenocarcinoma tissues. Demethylation treatment of HeLa dramatically increased the expression of mature miR-9. Both in vitro and in vivo functional experiments confirmed that miR-9 can inhibit the proliferation, migration, and malignant transformation abilities of HeLa cells. Bioinformatics methods and array-based RNA expression profiles were used to screen the downstream target genes of miR-9. Dual-luciferase reporting assay, real-time qPCR, and ELISA or Western blot confirmed four genes (CKAP2, HSPC159, IL-6, and TC10) to be novel direct target genes of miR-9. Pathway annotation analysis of the differently expressed genes (DEGs) induced by ectopic miR-9 expression revealed the enrichment in Jak/STAT3 pathway, which is one of the downstream pathways of IL-6. Ectopic expression of miR-9 in HeLa inhibited Jak/STAT3 signaling activity. Moreover, such effect could be partially reversed by the addition of exogenous IL-6. In conclusion, our results here present a tumor suppressor potential of miR-9 in cervical adenocarcinoma for the first time and suggest that miR-9 could repress tumorigenesis through inhibiting the activity of IL-6/Jak/STAT3 pathway.
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