Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain

Table 6 In vivo and in vitro exposure paradigms converge with human data on same cellular functions

Humans			Rat drinking models						Mouse neural stem cells
Serum			3 week daily serum			3 week binge serum			FGF2 + EtOH-treated			TGFβ1 + EtOH-treated
Functional group	p-value	# Mol	Functional group	p-value	# Mol	Functional group	p-value	# Mol	Functional group	p-value	# Mol	Functional group	p-value	# Mol
Cellular development^a	1.77 × 10⁻³	3	Cellular development^a	1.10 × 10⁻¹⁰	32	Cellular development^a	8.32 × 10⁻¹⁸	35	Cellular development^a	2.64 × 10⁻¹²	49	Cell death and survival^a	4.37 × 10⁻⁷	12
Cell death and survival^a	2.36 × 10⁻³	4	Cell growth and proliferation^a	1.10 × 10⁻¹⁰	27	Cell growth and proliferation^a	8.32 × 10⁻¹⁸	34	Cell growth and proliferation^a	9.86 × 10⁻⁵	42	Cellular development^a	1.33 × 10⁻⁵	13
Cell morphology	4.72 × 10⁻³	1	Cell death and survival^a	5.65 × 10⁻⁸	26	Cell death and survival^a	6.89 × 10⁻¹⁰	27	Cell cycle	1.82 × 10⁻⁴	18	Cell growth and proliferation^a	1.33 × 10⁻⁵	13
Cell function and maintenance	4.71 × 10⁻³	1	Cellular movement	1.15 × 10⁻⁵	18	Cell cycle	1.68 × 10⁻⁷	16	Cellular movement	1.82 × 10⁻⁴	27	Cell cycle	1.88 × 10⁻⁵	9
Cellular growth and proliferation^a	1.47 × 10⁻²	2	Cell cycle	1.14 × 10⁻⁴	12	Cellular assembly and organization	5.94 × 10⁻⁵	5	Cell death and survival^a	1.07 × 10⁻³	17	Cell morphology	1.85 × 10⁻⁴	5

Ingenuity IPA analysis of significantly changed miRNAs found using RNA-sequencing (Tiers A and B) show top functional groups affected by ethanol in each experiment. Different ethanol exposure paradigms, both in vitro (in neural stem cells) and in vivo (in humans and rats), show complete convergence for 3 of the top 5 functional groups (^a) identified by IPA as affected by ethanol

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