Suppression of CX43 expression by miR-20a in the progression of human prostate cancer

Gap junctions and cancer: communicating for 50 years

“…For example, promoter hypermethylation of GJC1 encoding Cx45 was shown to reduce Cx45 expression in colon cancer cell lines and in colorectal tumours 93 . At the post-transcriptional level, several microRNAs (miRNAs) have been shown to downregulate Cx43 expression 91,92 , e.g., the miR-221/222 cluster and miR-125b in glioma 94,95 and miR-20a in prostate cancer 96 .…”

Regulation of Connexins Expression Levels by MicroRNAs, an Update

“…Regulation of Cxs through miRNAs has been well characterized in cancer. For example, in human prostate cancer, upregulation of miR-20a induces a reduction in Cx43 levels (Li et al, 2012). The authors also show that downregulation of miR-20a inhibitor (LentimiRa-Off-has-miR-20a Vector) suppresses the proliferation of MDA-PCa-2b cells, both in vivo and in vitro , and inhibits tumor growth in vivo (Li et al, 2012).…”

“…For example, in human prostate cancer, upregulation of miR-20a induces a reduction in Cx43 levels (Li et al, 2012). The authors also show that downregulation of miR-20a inhibitor (LentimiRa-Off-has-miR-20a Vector) suppresses the proliferation of MDA-PCa-2b cells, both in vivo and in vitro , and inhibits tumor growth in vivo (Li et al, 2012). Likewise, in glioblastoma multiforme, it was observed that downregulation of Cx43 by miR-221/222 is implicated in invasiveness and disease progression (Hao et al, 2012).…”

Possible role of hemichannels in cancer

“…Li et al (2012a,b) found an inverse relationship between miR-20a and Cx43 protein and mRNA expression in human prostate tumors and cell lines. In this model, downregulation of miR-20a caused a 4-fold increase in Cx43 expression and reduced the cell proliferation.…”

“…Later on, numerous studies confirmed the permeability of Cx hemichannels to ATP in diverse cell types and using an extensive repertoire of experimental conditions including the removal of extracellular divalents (Arcuino et al, 2002; Stout et al, 2002; Stout and Charles, 2003; Gomes et al, 2005; Pearson et al, 2005; Zhao et al, 2005; Bahima et al, 2006), mechanical stimulation (Arcuino et al, 2002; Stout et al, 2002; Gomes et al, 2005; Zhao et al, 2005; Richter et al, 2014), increased [Ca 2+ ] i (Braet et al, 2003a,b; De Vuyst et al, 2009), hypoxia/ischemic like conditions (Faigle et al, 2008; Clarke et al, 2009), membrane depolarization (Kang et al, 2008; Nualart-Marti et al, 2013), application of bacterial lypopolysaccharide (De Vuyst et al, 2007), treatment with amyloid beta peptide (Orellana et al, 2011), exposure to hypotonic stress (Lu et al, 2012), after spinal cord injury (Huang et al, 2012), in activated polymorphonuclear granulocytes (Eltzschig et al, 2006), induced by gamma irradiation (Ohshima et al, 2012) and after air-stimulation of cultured keratinocytes (Barr et al, 2013). Hemichannels formed by Panx1 have also been consistently shown to allow the passage of ATP in diverse cell types and experimental models (Bao et al, 2004; Locovei et al, 2006; Huang et al, 2007; Reigada et al, 2008; Schenk et al, 2008; Buvinic et al, 2009; Iglesias et al, 2009; Qiu and Dahl, 2009; Ransford et al, 2009; Chekeni et al, 2010; Garré et al, 2010; Murata et al, 2010; Sridharan et al, 2010; Woehrle et al, 2010; Seminario-Vidal et al, 2011; Dolmatova et al, 2012; Iglesias and Spray, 2012; Li et al, 2012a,b; Lohman et al, 2012; Sandilos et al, 2012; Xia et al, 2012; Xiao et al, 2012; Pinheiro et al, 2013; Riquelme et al, 2013b). Moreover, Panx1 hemichannels are functionally coupled to P2X and P2Y receptors activation (Locovei et al, 2006; Pelegrin and Surprenant, 2006; Wang et al, 2013a,b).…”