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Role of microRNAs in the process of metformin treating multiple diseases
doi: 10.2478/fzm-2021-0009
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Abstract:
Metformin as the first-line treatment for type 2 diabetes mellitus has been discovered to exert beneficial effects on many diseases for nearly ten years, but its specific mechanism is still unclear. As a new class of gene expression regulators with pleiotropic properties, microRNAs (miRNAs) participate in multiple physiological processes such as cell differentiation, proliferation, survival, and metabolism, which drive them to play a regulatory role in the occurrence, development and even treatment of various diseases. A substantial body of research has found the relationship between metformin and miRNAs, in which metformin can alter the expression profiles of miRNAs in multiple disease states and on the other hand the signal pathways involving miRNAs may contribute to the pharmacological actions of metformin. This review summarizes the effects of metformin on miRNAs and their relationship in different diseases (like tumor, metabolic diseases, etc.), which should be of a great help for our better understanding of the mechanism of metformin for treating multiple diseases.
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Key words:
- metformin /
- microRNA /
- tumor /
- metabolic diseases
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Table 1. List of miRNAs regulated by metformin with various cancers
Cancer Related miRNAs Metformin effects Target genes Cell line Lung cancer miR-381 Upregulate YAP A549, H1299, Calu6, H520 miR-7 Upregulate AKT/mTOR A549 Erk, NF-κB miR-222 Downregulate p27, p57 A549 PTEN NCI-H358 Pancreatic cancer miR-26a Upregulate HMGA1 Sw1990 Panc1 miR-200b Upregulate AsPC-1 AsPC-1-GTR MiaPaCa-2 miR-34a Upregulate Notch, Slug Panc02 miR-150 Upregulate Breast cancer miR-21-5p Downregulate SESN1 SUM159PT CAB39L MCF-7, BT-474 BT-549 miR-27a Downregulate AMPKα2 MCF-7 miR-26a Upregulate PTEN MDA-MB-231 MCL-1 MDA-MB-468 MTDH MCF-7 EZH2 miR-155 Downregulate miR-200c Upregulate c-Myc MDA-MB-231 AKT/Bcl-2 MCF-7 Let-7a Upregulate miR-96 miR-181a Downregulate miR-193b Upregulate FASN MDA-MB-231 MDA-MB-468 BT-549 Renal cell miR-26a Upregulate Bcl-2 786-O carcinoma Cyclin D1 miR-21 Downregulate PTEN CAKI-1 CAKI-2 Oral Cancer miR-26a Upregulate Mcl-1 KB cell Skin cancer miR-21 Downregulate PTEN/AKT HaCaT Colon cancer miR-21 Downregulate PTEN/AKT HuTu80 miR-1915 Upregulate Bcl-2 HuTu80 Cervical cancer miR-142-3p Upregulate HMGA2 SiHa HeLa Esophageal miR-497 Upregulate PELP1 ESCC squamous cell carcinoma Osteosarcom a miR-570-3p Upregulate LCMR1 143B ATG12 U2OS 
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Table 2. List of miRNAs regulated by metformin for treating glycolipid metabolic disease
Metabolic Disease Related miRNA Metformin effects Target genes Cell line T2DM miR-140-5p Downregulate miR-222 Downregulate miR-142-3p Upregulate miR-192 Upregulate miR-33b Downregulate CPT1 HepG2 CROT miR-291-3b Downregulate AMPKα1 NCTC1469
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Table 3. Lists of miRNAs involved in metformin treating other diseases
Disease Related miRNA Metformin effects Target genes Cell line Anti-angioge nesis miR-21 Downregulate PTEN, HUVEC SMAD7 miR-221/222 Upregulate p27Kip1 miR-34a Downregulate Sirtuin1 MMEC Atheroscleros is Inflammation miR-124 Downregulate P4Hα1 VSMC miR-34a-5p Upregulate RAW264.7 miR-125b-5p miR-146a Upregulate miR-99b Upregulate AKT miR-155 Downregulate AKT miR-206 Downregulate HDAC4/ cyclin D1
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