Table 1 The 19 miRNAs significantly upregulated (two-fold or more) in cortical neurons 12 h coculturing with OGD-IEC-6 cells (determined by qRT-PCR).

From: Ischemia/reperfusion injured intestinal epithelial cells cause cortical neuron death by releasing exosomal microRNAs associated with apoptosis, necroptosis, and pyroptosis

microRNA	KEGG pathway target gene	Fold changes [compared to (Control-IEC-6) group]					Gene function (reference)
microRNA	KEGG pathway target gene	OGD-IEC-6+37 °C	OGD-IEC-6+32 °C	Control-Neuron+37 °C	OGD-IEC-6+Neuron+37 °C	OGD-IEC-6+Neuron+32 °C	Gene function (reference)
rno-miR-384-5p	Ppp3cb Pik3r2 Casp3 Prkar2b Casp8 Tp53 Il1a Pik3cd Ppp3r1	164.6*	125.4	35.6	783.0^†	267.7^‡	Enhances ER stress-induced cell apoptosis, and upregulates cleaved caspase-3 expression¹⁶
rno-miR-136-5p	Ppp3r2 Ppp3r1 Fadd Chuk	119.9*	67.7	18.1	629.5^†	88.0^‡	Modulates the inflammatory and immune responses and downregulates Bcl-2¹⁷
rno-miR-9a-5p	Bcl2 Ikbkb Prkar2b CFLAR Cyct Dffa Pik3cd Nfkb1 Irak1 Capn1	67.4*	100.2	49.6	403.9^†	239.7^‡	Increases the levels of pro-apoptotic regulator Fas ligand (FasL)¹⁹
rno-miR-369-3p	Tnf Bcl2 Casp3 Prkx Il1a Ngf Casp6 Ppp3r1	35.8*	5.7	40.6	248.0^†	25.3^‡	Induces apoptosis as well as aberrant TNFα production ²¹
rno-miR-449a-5p	Bcl2 Prkar2b Tp53 Dffb Fadd Rela	60.2*	1.9	9.8	200.3^†	1.6^‡	Induces apoptosis by regulating cyclin D1 and Bcl-2 expression²²
rno-miR-410-3p	Prkar2b	26.3*	18.8	24.5	141.9^†	83.3^‡	Down-regulates the expression of IL-10 through targeting STAT3²³ and induces apoptosis by targeting high-mobility group box 1 protein (HMGB1)²⁴
rno-miR-497-5p	Tradd Il1rap Ripk1 Ikbkb Prkx Cyct Irak2 Prkar2a Dffb Bcl2l1 Map3k14 Nfkb1 Fadd	53.6*	33.7	6.2	107.1^†	23.1^‡	Induces apoptosis via the Bcl-2/Bax-Caspase9-Caspase3 pathway²⁵
rno-miR-539-5p	Ripk1 Prkx Prkar2b Casp9 Myd88 Ppp3r1 Chuk	15.1*	6.1	11.7	104.3^†	26.6^‡	Promotes apoptosis via activation of caspase-3 and suppression of the expression of ERK/AKT and mTOR²⁶
rno-miR-29b-3p	Tradd Birc2 Faslg Dffb Tnfrsf1a Casp6 Rela	22.2*	24.7	1.9	90.8^†	12.6^‡	Increases the protein level of cleaved caspase‐3 and the protein ratio of Bcl-2 to Bax²⁷
rno-miR-34a-5p	Bcl2 Fadd	28.5*	57.3	3.2	60.7^†	38.0^‡	Increases caspase-3 and caspase-9 activation and supresses Bcl-2 expression¹⁸
rno-miR-26b-5p	Ppp3cb	25.2*	2.2	1.4	57.5^†	1.9^‡	Increases apoptosis by repression of β‐catenin, and Bcl‐2³⁰
rno-miR-98-5p	Il1a Ngf	13.5*	6.2	0.9	32.5^†	5.2^‡	Regulates Fas expression and the sensitivity of Fas-mediated apoptosis³¹
rno-miR-152-3p	Chuk	13.7*	10.1	1.0	28.6^†	10.8^‡	induces apoptosis by Caspase-3 and Faslg²⁷
rno-miR-140-5p	Bcl2l1	13.0*	2.7	1.9	27.8^†	1.4^‡	Facilitates the autophagy³² and suppresses the TGF-β1 pathway through targeting Smad3³³
rno-miR-20b-5p	Map3k14 Ppp3r1	9.0	4.1	1.7	21.3^†	3.4^‡	Activates the TGF-β signalling pathway³⁴
rno-miR-20a-5p	Irak2 Map3k14 Ppp3r1	8.9	7.7	1.5	21.0^†	6.0^‡	Mitigates autophagy through suppressing autophagy-related gene 7 (ATG7)³⁵ and increases caspase-3 and caspase-9 expression³⁶
rno-miR-17-5p	Irak2 Map3k14 Ppp3r1	8.6	4.5	1.5	19.0^†	3.6^‡	Suppresses the apoptotic protease activating factor 1 (Apaf-1) expression³⁷
rno-miR-323-3p	Dffb Chuk	4.4	2.1	3.7	11.8^†	10.3^‡	Suppresses expression of SMAD2 and SMAD3 leading to inactivation of TGF-β signaling³⁸ and lowers caspase-3 expression³⁹
rno-miR-448-3p	Bcl2 Prkx Prkar2b	2.5	1.1	1.5	9.4^†	3.7^‡	Promote apoptosis of nerve cells by downregulating SIRT1³⁵

Data from 8 (12-well) plates of the intestinal epithelial cell-6 did not undergo oxygen-glucose deprivation (OGD) (Control-IEC-6 group), 8 (12-well) plates of IEC-6 cell undergo OGD and cultured at 37 °C (OGD-IEC-6+37 °C group), 8 (12-well) plates of IEC-6 cell undergo OGD and cultured at 32 °C (OGD-IEC-6+32 °C group), 8 (12-well) plates of neurons did not undergo OGD and cultured at 37 °C (Control-Neuron group), 8 (12-well) plates of IEC-6 cell undergo OGD then cocultured with neuron at 37 °C (OGD-IEC-6+Neuron+37 °C group), 8 (12-well) plates of IEC-6 cell undergo OGD then cocultured with neuron at 32 °C (OGD-IEC-6+Neuron+32 °C group). The fold increase for each parameter for the control-IEC-6 group is “1”.
OGD, oxygen-glucose deprivation; Caspase, cysteine-containing aspartate-specific protease; ER, endoplasmic reticulum; ADAM10, Bcl-2, B-cell lymphoma 2; STAT3, signal transducer and activator of transcription 3; HMGB1, high-mobility group box 1 protein; ATG5, autophagy-related 5; AREs, adenosine- and uridine-rich elements; Bax, Bcl-2-associated X protein; ERK, extracellular signal-regulated kinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; ADAM10, A Disintegrin and Metalloproteinase 10; SOX, SRY-related HMG-box; SIRT1, Sirtuin 1; TGF-β, transforming growth factor-beta; IRE1α, inositol-requiring enzyme-1 alpha; TXNIP, thioredoxin-interacting protein; SMAD, small mothers against decapentaplegic; Apaf-1, apoptotic protease activating factor 1.
Only significant and annotated transcripts are indicated.
*OGD-IEC-6-37 °C vs. Control-IEC-6-37 °C.
^†OGD-IEC-6+Neuron-37 °C vs. Control-IEC-6-37 °C, Control-Neuron-37 °C, or OGD-IEC-6-37°C.
^‡OGD-IEC-6+Neuron-37 °C vs. OGD-IEC-6+Neuron-32 °C.

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Table 1 The 19 miRNAs significantly upregulated (two-fold or more) in cortical neurons 12 h coculturing with OGD-IEC-6 cells (determined by qRT-PCR).

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