3p22.2

MIR26A,MIRN26A1,mir-26a-1

Hepatocellular carcinoma (HCC)

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).

Nasopharyngeal carcinoma (NPC)

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 p14^ARF and p21^CIP1 in an EZH2-dependent manner.

Breast cancer

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.

Rhabdomyosarcoma

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).

Airway smooth muscle hypertrophy

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.

Myogenesis

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).

Osteogenic differentiation

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).