19p13.13

MIRN23A,hsa-mir-23a,miRNA23A,mir-23a

Hepatocellular carcinoma

In the study by Huang et al. (2008), up-regulation of the cluster hindered TGF-β induced apoptotic cell death and supported cell growth in hepatocellular carcinoma. Activation of miR-23a by STAT-interleukin 6 negatively regulated PGC-1a and glucose-6-phosphatase catalytic subunit (G6PC), leading to decreased glucose production that favours hepatocellular carcinoma (Wang et al., 2012). Coptidis Rhizoma (CR, huanglian in Chinese) and its active compound, berberine has been shown to elicit anti-cancer properties in different cell lines and animal models (Wang et al., 2010; Feng et al., 2011). Zhu et al. (2011) has reported up-regulation of miR-23a after treatment with CR in hepatocellular carcinoma (HCC) cell lines, suggesting miR-23a can be one of the targets and biomarker alter for CR treatment in HCC cell lines and implying the potential application of CR on treatment of HCC.

Saumet et al. (2009) has observed PML-RARA oncogene dependent characteristic of miR-23a cluster and significant repression of miR-23a by PML-RARA. The association of retinoic acid receptor alpha (RARA) gene with promyelocytic leukemia (PML) protein in chromosomal translocation process favoured the protein expression in acute promyelocytic leukemia (APL).

Other cancers

Increased expression of miR-23a has been reported to promote cancer growth in bladder cancer, gastric adenocarcinoma and colorectal cancer (Mi et al., 2007; Gottardo et al., 2007; Zhu et al., 2010; Jahid et al., 2012).

Angiogenesis

Suppression of angiogenesis in vitro and postnatal retinal vascular development in vivo was reported in response to the reduced expression of miR-23. Loss of miR-23 gene has hindered laser-induced choroidal neovascularization in mouse model. These functions were postulated to be caused by the inhibition of Sprouty2 and Sema6A, which negatively regulate MAPK and VEGFR2 factors (Zhou et al., 2011). Poliseno et al. (2006) has stated the presence of receptors of angiogenic factors in human umbilical vein endothelial cells (HUVECs) as target of miR-23a.

Neural differentiation

A study by Kawasaki and Taira (2003) has demonstrated the regulation of Hes-1 gene by miR-23, thereby supporting the neuronal differentiation of NT-2 cells at post-transcriptional level. The reduced expression of miR-23 is associated with accumulation of Hes1 gene, a basic helix loop helix differentiation suppressor, resulting in blockage of retinoic acid induced neuronal differentiation.

Muscular atrophy / Cardiac hypertrophy

The miR-23a inhibited translation of muscle-specific ubiquitin ligases, MAFbx/atrogin-1 and muscle RING-finger 1 (MuRF1), thus promoting protection against skeletal muscle atrophy (Wada et al., 2011). In the report by Lin et al. (2008), nuclear factor of activated T cells (NFATc3) is proposed to regulate cardiac hypertrophy by transcriptionally activate miR-23a. Muscle RING-finger 1 (MuRF1) is the target of miR-23a where hypertrophic signal is conveyed by miR-23a through suppressing the translation of MURF1.

Development of primary hematopoietic cells

Inhibition of B lymphopoiesis both in vitro and in vivo by miR-23a cluster expressing hematopoietic progenitor was reported by Kong et al. (2010). The cluster was recognised as the downstream target of transcription factor PU.1. PU.1 has four conserved binding sites for promoter of miR-23a cluster. It showed that the cluster promoted myelopoiesis, while blocked the development of B lymphoid cells.