MicroRNAs, stem cells and cancer stem cells

Table 1 miRNA mediated regulation in the maintenance and function of stem cells

miRNA	Functions in stem cells	Mechanism(s)	Ref.
Pluripotent miRNAs
miR-290 cluster, miR-370, miR-302	Promotes self-renewal	Regulate embryonic stem cell cycle	[32]
miR-141, miR-200, miR-429	Maintenance of self-renewal in the absence of leukemia inhibitory factor	Regulated by cMyc proteins	[66]
miR-9	Proliferation and promote NSC migration	Target Stmn1, which increases microtubule instability	[67]
	Neurite outgrowth	Inhibit Cdc42 expression and altering the localization of Rac1
miR-184	NSC proliferation	Represses the expression of Numb-like 1	[68]
miR-137	Promotes NSC proliferation but inhibits neuronal maturation, dendritic morphogenesis, and spine development	Target Mind bomb 1, an ubiquitin ligase	[69]
Pro-differentiation miRNAs
miR-134, miR-145, miR-296, miR-470	Initiate differentiation	Suppress pluripotent markers including Nanog, Oct4, Sox, Klf4	[33]
Let-7	Stabilize differentiation	Target transcripts that are regulated by the pluripotency transcription factors Oct4, Sox2, Nanog and Tcf3	[34]
		Promote somatic cell cycle by targeting both directly and indirectly the multiple activators of the G1-S transition including cdc25a, cdk6, cyclinD1 and cyclinD2	[35-37]
miR-124	NSC differentiation	Suppress Sox9 expression in adult NSCs and exhibit mutual inhibition mechanism of Ephrin-B1	[70]

Let-7: Lethal-7; NSC: Neuronal stem cell; Sox: Sex-determining region Y-box containing gene.

Table 2 Aberrant miRNA expression in cancer stem cell

miRNA	Tumor type	Mechanism(s)	Ref.
miRNA as oncomiR
miR-17-92 polycistron	Upregulated in lung, breast, stomach, prostate, colon and pancreatic cancers	Regulate c-Myc expression	[46,47]
miR-21, miR-205	Head and neck cancer	Target transcripts of tumor suppressive genes including kinesin family member 1B isoform α, hypermethylated in cancer 2, and pleomorphic adenoma gene 1	[71]
miR-372, miR-373	Testicular germ cells	Neutralize p53-mediated CDK inhibition, possibly through direct inhibition of the expression of the tumor-suppressor LATS2	[72]
miR-21	Breast cancer	Target tumor suppressor tropomyosin 1	[73]
miR-126	Gastric carcinoma	Targets SOX2, and PLAC1	[48]
Let-7	Hepatocellular carcinoma	Targets SOCS1, caspase-3	[56]
miR-181	Hepatocellular carcinoma	Targets RASSF1A, TIMP3 as well as nemo-like kinase	[56]
miR-495	Breast cancer	Modulated by transcription factor E12/E47, suppresses E-cadherin expression to promote cell invasion and inhibits regulated in development and DNA damage responses 1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism	[74]
miRNAs as tumor suppressors
Let-7	Colon adenocarcinomas	Target Lin-28b which promotes cell migration, invasion and transforms immortalized colonic epithelial cells	[50]
miR-15 miR-16 cluster	Chronic lymphocytic leukemia	Targets the apoptotic inhibitor Bcl-2	[47]
miR-29	Cholangiocarcinoma	Regulate the anti-apoptotic protein Mcl-1	[75]
miR200c	Head and neck squamous cell carcinoma	Negatively modulates the expression of BMI1 and ZEB1	[62]
miR-125b	Glioma	Decreases the cell cycle regulated proteins CDK6 and CDC25A	[76]

Let-7: Lethal-7; SOX2: Sex-determining region Y-box 2; PLAC1: Placenta-specific 1 gene.