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| Entity | Hepatocellular carcinoma (HCC) |
| Note | MIR26A is reduced in hepatocellular carcinoma and directly suppresses the expression of ERα (estrogen receptor alpha, ERα) (Chen et al., 2011), cyclin D2 and cyclin E2 (Kota et al., 2009). The overexpression of MIR26A negatively regulates cell proliferation (Chen et al., 2011) and cell cycle (Kota et al., 2009). Systemic administration of MIR26A in a mouse model of HCC using adeno-associated virus (AAV) results in inhibition of cancer cell proliferation, induction of tumor-specific apoptosis, and dramatic protection from disease progression without toxicity (Kota et al., 2009). |
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| Entity | Nasopharyngeal carcinoma (NPC) |
| Note | MIR26A is commonly downregulated in NPC specimens and NPC cell lines and directly suppresses the expression of EZH2 (enhancer of zeste homolog 2, EZH2) (Lu et al., 2011). Ectopic expression of MIR26A inhibits growth and colony formation of NPC cells by inducing G1-phase cell-cycle arrest. MIR26A also suppresses tumorigenesis of NPC cells in vivo. MIR26A suppressed the expression of c-myc, cyclins D3 and E2, and cyclin-dependent kinases CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14ARF and p21CIP1 in an EZH2-dependent manner. |
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| Entity | Breast cancer |
| Note | MIR26A is downregulated in breast cancer specimens and cell lines and directly regulates the expression of MTDH (metadherin, MTDH) and EZH2 (Zhang et al., 2011). MIR26A leads to apoptosis, inhibition of colony forming and in vivo tumorigenesis of breast cancer cells. |
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| Entity | Rhabdomyosarcoma |
| Note | In rhabdomyosarcoma, MIR26A is underexpressed while the mRNA of EZH2 is increased. EZH2 is one of direct targets of MIR26A in several different cell lines (Ciarapica et al., 2009; Lu et al., 2011; Zhang et al., 2011). |
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| Entity | Airway smooth muscle hypertrophy |
| Note | Stretch selectively induces the transcription of MIR26A in human airway smooth muscle cells (HASMCs). The transcription factor CCAAT enhancer-binding protein α (C/EBPα) directly activates miR-26a expression through the transcriptional machinery upon stretch. Glycogen synthase kinase-3β (GSK-3β) is a direct target of MIR26A (Mohamed et al., 2010). The enforced expression of MIR26A induces HASMC hypertrophy. |
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| Entity | Myogenesis |
| Note | MIR26A is up-regulated during myogenesis and directly targets EZH2. Overexpression of MIR26A in murine myogenic C2C12 cells induced creatine kinase activity. Moreover, myoD and myogenin mRNA expression levels were also up-regulated. Therefore, increased expression of miR-26a promotes myogenesis (Wong and Tellam, 2008). |
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| Entity | Osteogenic differentiation |
| Note | During hADSC (human adipose tissue-derived stem cells, hADSCs) differentiation, MIR26A shows increased expression. The inhibition of miR-26a increases protein levels of its predicted target, SMAD1 transcription factor (Luzi et al., 2008). |
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| Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and -independent pathways. |
| Chen L, Zheng J, Zhang Y, Yang L, Wang J, Ni J, Cui D, Yu C, Cai Z. |
| Mol Ther. 2011 Aug;19(8):1521-8. doi: 10.1038/mt.2011.64. Epub 2011 May 24. |
| PMID 21610700 |
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| Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. |
| Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, Giordano A. |
| Cell Cycle. 2009 Jan 1;8(1):172-5. Epub 2009 Jan 30. |
| PMID 19106613 |
| |
| MicroRNA expression, survival, and response to interferon in liver cancer. |
| Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. |
| N Engl J Med. 2009 Oct 8;361(15):1437-47. |
| PMID 19812400 |
| |
| Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. |
| Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT. |
| Cell. 2009 Jun 12;137(6):1005-17. |
| PMID 19524505 |
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| MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. |
| Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, Chen YC, Peng Y, Yao KT, Kung HF, Li XP. |
| Cancer Res. 2011 Jan 1;71(1):225-33. |
| PMID 21199804 |
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| Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. |
| Luzi E, Marini F, Sala SC, Tognarini I, Galli G, Brandi ML. |
| J Bone Miner Res. 2008 Feb;23(2):287-95. |
| PMID 18197755 |
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| Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3b. |
| Mohamed JS, Lopez MA, Boriek AM. |
| J Biol Chem. 2010 Sep 17;285(38):29336-47. Epub 2010 Jun 3. |
| PMID 20525681 |
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| MYC stimulates EZH2 expression by repression of its negative regulator miR-26a. |
| Sander S, Bullinger L, Klapproth K, Fiedler K, Kestler HA, Barth TF, Moller P, Stilgenbauer S, Pollack JR, Wirth T. |
| Blood. 2008 Nov 15;112(10):4202-12. Epub 2008 Aug 19. |
| PMID 18713946 |
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| MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. |
| Witwer KW, Sisk JM, Gama L, Clements JE. |
| J Immunol. 2010 Mar 1;184(5):2369-76. Epub 2010 Feb 3. |
| PMID 20130213 |
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| MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis. |
| Wong CF, Tellam RL. |
| J Biol Chem. 2008 Apr 11;283(15):9836-43. Epub 2008 Feb 15. |
| PMID 18281287 |
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| Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. |
| Zhang B, Liu XX, He JR, Zhou CX, Guo M, He M, Li MF, Chen GQ, Zhao Q. |
| Carcinogenesis. 2011 Jan;32(1):2-9. Epub 2010 Oct 15. |
| PMID 20952513 |
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