Table 1 List of predicted target mRNAs by analysis of miRNAs in EVs derived from the co-culture media (AD-H:AD, BM-H:BM, TM-H:TM)

(a) Predicted target genes on the increased expression of miRNA under three conditions (AD-H:AD, BM-H:BM, TM-H:TM)

miR-3960

POU3F3

POU class 3 homeobox 3

Regulation of oncogenic signaling pathway

Interaction with SMAD protein and the tumor suppressor PTEN

VP_5455

[42]

Pcdha2

Protocadherin alpha 2

Establishment and function of specific cell-cell connections.

Demonstrate an organization similar to that of B-cell and T-cell receptor gene

ExoCarta_393086

VP_393086

[43]

CERS1

Ceramide synthase 1

Encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide

Encodes growth differentiation factor from a monocistronic mRNA

ExoCarta_10715

VP_10715

[44]

EGR

Early growth response

May also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development

ExoCarta_13654

VP_1959

[45]

MIF

Macrophage migration inhibitory factor

Encodes a lymphokine involved in immunoregulation, cell-mediated immunity, and inflammation

ExoCarta_4282

VP_4282

[46]

(b) Predicted target genes on the increased expression of miRNA under two conditions (BM-H:BM, TM-H:TM)

miR-5787

PACS1

Phosphofurin acidic cluster sorting protein 1

Plays a role in Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling harmful factors to escape immune surveillance

ExoCarta_107975

VP_107975

[47]

PPP1R7

Protein phosphatase 1 regulatory subunit 7

Encodes a protein subunit that regulates the activity of the serine/threonine phosphatase, protein phosphatase-1

ExoCarta_5510

VP_5510

[48]

VSX2

Visual system homeobox 2

Encodes a homeobox protein originally described as a retina-specific transcription factor

ExoCarta_338917

VP_338917

[49]

SMAD2, SMAD3

SMAD family member 2, SMAD family member 3

Functions in the transforming growth factor-beta signaling pathway

Cell proliferation, tumor suppressor

ExoCarta_4088

VP_4088

[50]

SYT1

Synaptotagmin I

Ca(2+) sensors in the process of vesicular trafficking and exocytosis

ExoCarta_6857

VP_6857

[51]

(c) Predicted target genes on the increased expression of miRNA on BM-H:BM

miR-638

ADGRE5

Adhesion G protein-coupled receptor E5

Involved in both adhesion and signaling processes early after leukocyte activation

ExoCarta_976

[46]

SLC25A23

Solute carrier family 25-member 23

Decreases mitochondrial Ca (2+) uptake and reduces cytosolic Ca (2+) clearance after histamine stimulation

ExoCarta_79085

VP_79085

[51]

Cela3b

Chymotrypsin-like elastase family, member 3B

Functions in the intestinal transport and metabolism of cholesterol

Little elastolytic activity

ExoCarta_67868

VP_67868

[47]

KDSR

3-ketodihydrosphingosine reductase

Catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine

ExoCarta_2531

VP_2531

[55]

EMILIN3

Elastin microfibril interfacer 3

Developing gonads and osteogenic mesenchyme

ExoCarta_90187

VP_90187

[56]

(d) Predicted target genes for miRNa with increased expression on BM-H:BM,TM-H:TM and miRNA with decreased on AD-H:ADM

miR-320e

LAPTM4A

Lysosomal protein transmembrane 4 alpha

Transport of small molecules across endosomal and lysosomal membranes.

ExoCarta_9741

VP_9741

[57]

PNRC1

Proline-rich nuclear receptor coactivator 1

RNA polymerase (pol) II-transcribed genes by functioning as a nuclear receptor coactivator

ExoCarta_10957

VP_10957

[50]

SKA3

Spindle and kinetochore associated complex subunit 3

Component of the spindle and kinetochore-associated protein complex that regulates microtubule attachment to the kinetochores during mitosis

VP_221150

[46]

TMEM47

Transmembrane protein 47

Localized to the ER and the plasma membrane

ExoCarta_83604

VP_83604

[58]

SEMA6D

Sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D

Secreted and membrane associated proteins

Axon pathfinding, fasciculation and branching, and target selection

VP_80031

[59]

miR-8075

TMOD2

Tropomodulin 2

Actin-capping protein for the slow-growing end of filamentous actin

ExoCarta_29767

VP_29767

[22]

ADCY1

Adenylate cyclase 1

Adenylate cyclase gene family that is primarily expressed in the brain

Ca(2+)/calmodulin concentration

ExoCarta_107

VP_107

[48]

CD1B

CD1b molecule

Primarily lipid and glycolipid antigens of self or microbial origin to T cells

ExoCarta_910

VP_910

[60, 61]

OLFM1

Olfactomedin 1

Neurogenesis, neural crest formation, dorsal ventral patterning, cell-cell adhesion

Cell cycle regulation, tumorigenesis, and signaling pathways (Wnt, BMP)

VP_10439

[62, 63]

PRTG

Protogenin

Development of various tissues, especially neurogenesis

VP_283659

[46]

miR-6732-5p

OAS2

2’-5’-Oligoadenylate synthetase 2, 69/71 kDa

Innate immune response to viral infection

ExoCarta_4939

VP_4939

[61]

STX17

Syntaxin-17

Control of autophagosome membrane fusion with the lysosome membrane

[63]

KLK3

Kallikrein related peptidase 3

GPCR signaling pathways, translation Non-genomic (rapid) action of androgen receptor.

VP_354

[64]

DYNC1LI1

Dynein, cytoplasmic 1, light intermediate chain 1

Intracellular vesicle trafficking

ExoCarta_51143

[65]

ABCC5

ATP-binding cassette, sub-family C (CFTR/MRP), member 5

Resistance to thiopurine anticancer drugs, 6-mercaptopurine and thioguanine functions

ExoCarta_10057

VP_10057

[66]

miR-2115-5p

ATL3

Atlastin GTPase 3

Network of interconnected tubules of the endoplasmic reticulum

ExoCarta_25923

VP_25923

[67]

USP49

Ubiquitin specific peptidase 49

Epigenetic transcriptional activation and acts as a regulator of mRNA splicing.

ExoCarta_25862

VP-25,862

[46]

TTPAL

Alpha tocopherol transfer protein like

Stimulates the movement of vitamin E between membrane vesicles in vitro and facilitates the secretion of tocopherol from hepatocytes

N/D (Not detected)

[68]

CERS6

Ceramide synthase 6

Cell proliferation, differentiation, apoptosis, and senescence

ExoCarta_253782

VP_253782

[69]

CD247

CD247 molecule

Encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells, and various types of tumor cells

ExoCarta_919

VP_919

[70]