Table 2.

Evidence of miRNAs to function as distal regulators for gene expression

miRNA Source	miRNA ID	Studied objects	Administrating/ Intervening methods	Corresponding change of expression level in target issue/cells	Observed functions	References
Endogenous miRNA
MV secreted by u87-MG astrocytes	miR-34a	SH-SY5Y cell/ 6-OHDA model rats	Co-culture with MV/inject	miR-34a was significantly increased in SH-SY5Y cells/unclear	Targeting anti-apoptotic Bcl-2 proteins,enhances the sensitivity of dopaminergic neurons to neurotoxins and accelerates neuronal injury	(Mao et al. 2015)
Human cytomegalovirus	miR- UL148D	Kasumi-3 cell and CD34 + hematopoietic stem cells	Co-culture with strain NR-1	Significantly increase	Target IER5 and promote viral latency through iER5-CDC25B-CDK1 signaling pathway	(Pan et al. 2016)
MV secreted by Lewis lung cancer	miR-214	CD4+T cell /BALB/c nude mice	Co-culture/tail vein injection with fluorescent labeled MV	Significantly increase/Fluorescence markers were found in nude mice	Target PTEN.down-regulate PTEN-mediated signal cascade to promote Treg cell amplification and tumor growth	(Yin et al. 2014)
Exsome secreted by MCF-7 and MDA-MB-231 cell	miR-222	MCF-7 cell/ Female nude mice	Co-culture with exosomes/subcutaneous injection	Confocal microscopy images indicate exosome uptake / unclear	Target NF-KB promotes cell invasion and migration, and promotes tumor growth	(Ding et al. 2018)
Exsome secreted by HCT-116 and SW480	miR-200b	HCT-116 and SW480 cell/BALB/c males mice	Co-culture with Exo-miR-200b/inject	Significantly increase/Immuno fluorescence analysis increased	Target P27 and RND3, promote colorectal cancer growth	(Zhang et al. 2018)
Exsome secreted by HCC cell	miR-21	LX2 cell/Female nude mice	Co-culture with exosomes/Caudal vein injection	increase/unclear	activate HSC through the PTEN/PDK1/AKT signaling axis,promote liver fibrosis, tumor growth and angiogenesis	(Zhou et al., 2018)
Exsome secreted by MCF-7̖;HCC-1937 and MDA-MB-231 cells	miR‑7641	MCF-7̖;HCC-1937̖;MDA-MB-231̖;Primary breast cancer cell/BALB/c Female nude mice	Transfection/intravenous injection	increase/unclear	Promote breast tumor cell proliferation, increase its invasiveness, promote tumor metastasis	(Shen et al. 2021)
Herbs
HS decoction̖;Synthetic miR-2911	miR-2911	MDCK cell /BALB/c mice	Co-culture with decoction total RNA or synthetic miR-2911/gavage	unclear/ Plasma, lung and liver tissues of mice were detected	Inhibit the replication of H1N1, H5N1 and H7N9 viruses and significantly reduce the mortality caused by virus infection	(Zhou et al. 2015)
HS decoction	miR-2911	Pregnant mice	gavage	Plasma, placenta and fetal liver of pregnant mice miR2911 Significantly increase	Regulate fetal growth and development	(Li et al. 2015)
Exosomes from cells transfected with miR-2911 or HS decoction	miR-2911	Vero E6 cell/ Healthy volunteers	Co-culture with exosome/ oral	miR-2911 was elevated in Vero E6 cells and serum of volunteers	Inhibit novel Coronavirus SARS-COV-2 replication and accelerate negative conversion in patients with COVID-19	(Zhou et al. 2020)
Synthetic astragalus miR-396	miR-396	BALB/ c asthmatic model mice	Nasal feeding	Peripheral blood, spleen and lung were significantly increase	Inhibit the expression of GATA-3 in Th2 cells	(Shen et al. 2019)
Plant food
Synthetic single strand mature miR-168a and fresh rice	miR-168a	HepG2 cell/mice	Co-culture with synthetic miR-168a/oral feeding	miR-168a was significantly elevated in HepG2 cells and mice	Target LDLRAP1 and promote LDL clearance	(Zhang et al. 2012)
Strawberry	FvmiR-168	Dendritic cell	Co-culture with FvmiR-168	increase	Strawberry miRNA acts on the Toll-like receptor of dendritic cells and inhibits their migration, thereby reducing inflammation	(Cavalieri et al. 2016)
MV secreted by healthy persons; Synthetic miR-159	miR-159	MDA-MB-231 cell /NSG mice	Co-culture with MV/ gavage	unclear/miR-159 was detected in the gastrointestinal tract	Target TCF7,inhibits breast tumor cell proliferation	(Chin et al. 2016)
Synthetic miR-156a	miR-156a	CNE2̖;HONE1̖;C666-1 cell	Co-culture with miR-156a mimic	unclear	Target JAMA,inhibit the development of nasopharyngeal carcinoma	(Tian et al. 2016)
vegetables	miR-156a	HAEC cell	Co-culture with miR-156a	Significantly increase	Inhibit JAMA expression in human aortic endothelial cells and reduce monocyte adhesion	(Hou et al. 2018)
Rape pollen	miR-162a	Bee larvae	oral feeding	miR-162a was detected in vivo	Target mTOR,delay the development of young bees, reducing body and ovarian size, and promoting their development into worker bees	(Zhu et al. 2017)
ELNs original ginger	aly-miR-396a-5p	Vero E6 cell / septic mouse model	Co-culture with aly-miR-396a-5p/Intratracheal injection	increase/ Fluorescence appeared in lung and serum of mice	Inhibit the expression of Novel Coronavirus spike protein and NSP12 protein respectively, reduce inflammation and apoptosis	(Teng et al. 2021)
Synthetic miR-159(rich in soybean)	gma-miR-159a	Hepatic stellate cell/hepatic fibrosis model ICR mice	Co-culture with fluorescent-labeled miR-159a/intraperitoneal injection	Fluorescent markers were observed either intracellular or in vivo	Target GSK-3β, inhibit the expression of GSK-3β and its downstream protein, alleviati liver fibrosis	(Yu et al. 2021)

HS: Honeysuckle; NSG: NOD-scid IL2Rgnull; HAEC cell: human aortic endothelial cell; JAMA: junction adhesion molecule-A; ELNs: exosome-like nanoparticles