ArticleFrontiers in oncology2021
Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Evaluation of miR-27a-5p and miR-449a as potential serum biomarkers for breast cancer: a combined bioinformatics and experimental study.Molecular biology reports · 2025Article
- Autophagy-related ncRNAs: Regulatory Roles and Potential Therapeutic Effects in Digestive System Neoplasms.Current medicinal chemistry · 2025Review
- miR-449, identified through antiandrogen exposure, mitigates functional biomarkers associated with ovarian cancer risk.Scientific reports · 2024Article
- miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.Cell biochemistry and biophysics · 2024Review
- Degradative autophagy regulates the homeostasis of miRnas to control cancer development.Autophagy · 2024Article
- Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis.International journal of molecular sciences · 2023Article
- Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.Biomolecules · 2023Review
- Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer.International journal of molecular sciences · 2023Review
- MicroRNA-nanoparticles against cancer: Opportunities and challenges for personalized medicine.Molecular therapy. Nucleic acids · 2023Review
- Methylation detection of circulating tumor cell miR-486-5p/miR-34c-5p in the progression of colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches.Cell communication and signaling : CCS · 2023Review
- FOXO1-Induced miR-502-3p Suppresses Colorectal Cancer Cell Growth through Targeting CDK6.Journal of oncology · 2023Article
- Secretory autophagy promotes Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1.Journal of biomedical science · 2022Article
- Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021.International journal of molecular sciences · 2022Review
- S-Adenosylmethionine Inhibits Colorectal Cancer Cell Migration through Mirna-Mediated Targeting of Notch Signaling Pathway.International journal of molecular sciences · 2022Article
- Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression.PeerJ · 2022Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.
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