MITF-M-dependent miR-211 expression

MIR211, encoding the microRNA miR-211 is an MITF-M-dependent target gene that is expressed in the melanocyte lineage and is frequently downregulated in melanoma (Hunter et al, 1998; Duncan et al, 1998; Duncan et al, 2001). The MIR211 gene falls in intron 6 of TRPM1, itself a direct MITF-M target, making MIR211 an co-transcriptional target (Miller et al, 2004; Miller et al, 2005; Strub et al, 2011). Both TRPM1 and miR-211 have been proposed as regulators of melanogenesis, but the precise roles played by each have not been clearly defined (Miler et al, 2004; Miller et al, 2005; Levy et al, 2010; Boyle et al, 2011; Margue et al, 2013; De Luca et al, 2016; reviewed in Goding and Arnheiter, 2019)<br>Genes regulated by miR-211 have diverse functions and disruption of expression of some of these target genes affects the invasiveness of melanoma cell lines (Levy et al, 2010; Boyle et al, 2011; Margue et al, 2013; De Luca et al, 2016). One miR-211 target is the transcription factor POU3F2 (also known as BRN2) which has been implicated in the regulation of MITF-M, establishing a feedback loop (Boyle et al, 2011; reviewed in Goding and Arnheiter, 2019; Fane et al, 2019).

MIR211基因编码的微小RNA miR-211是一种依赖MITF-M的靶基因，该基因在黑色素细胞谱系中表达，并且在黑色素瘤中经常出现下调现象（Hunter等，1998；Duncan等，1998；Duncan等，2001）。MIR211基因位于TRPM1基因的第6内含子中，而TRPM1本身是MITF-M的直接靶点，因此MIR211成为一个共转录靶点（Miller等，2004；Miller等，2005；Strub等，2011）。TRPM1和miR-211均被提议为黑色素生成过程的调节因子，但每个因子所扮演的精确角色尚未得到明确界定（Miler等，2004；Miller等，2005；Levy等，2010；Boyle等，2011；Margue等，2013；De Luca等，2016；详见Goding和Arnheiter，2019）。由miR-211调控的基因具有多样的功能，其中某些靶基因表达的中断会影响黑色素瘤细胞系的侵袭性（Levy等，2010；Boyle等，2011；Margue等，2013；De Luca等，2016）。miR-211的一个靶点是转录因子POU3F2（也称为BRN2），其在MITF-M的调控中发挥作用，形成了一个反馈回路（Boyle等，2011；详见Goding和Arnheiter，2019；Fane等，2019）。