Table 2.
MicroRNA/Aliases | Site of Interaction with GAS5 lncRNA | Tumor or Cell Type | Effect Demonstrated | Reference |
---|---|---|---|---|
miR-221/222 | Exon | Gliomas | Unknown | Zong et al., [49] |
miRNA-21 | Exon 5 * | Endothelial cells, ovarian carcinoma, cervical carcinoma | Reduced | Ma, et al. [36] Shen and She [86]; Wen et al. [39] |
miRNA-135b | Exon | Hepatocellular carcinoma (HCC) | Sponging or translational inhibition | Yang and Jiang [87]. |
miRNA-196a | GAS5 promoter ** or exon | Glioma, esophageal squamous cells | Downregulation of GAS5 RNA (Wang) | Wang et al. [83]; Zhao et al. [84] |
miRNA-137 | Exon | Melanoma | GAS5 RNA and miRNA co-regulated | Bian et al. [43] |
* It is claimed [86] that the target of miRNA-21 is the 22-nucleotide region of GAS5 (5′-ACAGGCATTAGACAGAAAGCTG-3′-OH; their Figure 1). This target lies completely within human exon 5 (the exon between SNORD77 and SNORD44); this exon (our Figure 1) harbors a putative small open reading frame. In protein-coding conventional mRNAs, microRNAs usual bind 3′-UTRs, although unconventional miRNA binding to ORFs has occasionally been observed. The authors of this 2018 publication make no comment on any proposed ORF. ** It is claimed [84] that miRNA-196a (highly expressed in glioblastoma multiforme), instead of serving as a post-transcriptional regulator, can be an epigenetic regulator and binds to a region of the GAS5 promoter which can be occupied by the transcription factor FOXO1, a TATTTT motif in the GAS5 promoter, presumably shutting down transcription of the tumor suppressor GAS5. This finding is consistent with numerous reports of short RNAs serving as epigenetic regulators at promoters [88].