The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends

Xiong, Linjin; Wei, Yumeng; Jia, Qiang; Chen, Jinglin; Chen, Tao; Yuan, Jiyuan; Pi, Chao; Liu, Huiyang; Tang, Jia; Yin, Suyu; Zuo, Ying; Zhang, Xiaomei; Liu, Furong; Yang, Hongru; Zhao, Ling

doi:10.1186/s12951-023-01888-1

Table 1 Role of cargoes in EVs in regulating metastasis in CRC

From: The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends

non-coding RNA/protein/gene	Source	Expression pattern	Action target/pathway	Outcome	References
a. Promote cancer progression
miR-27b-3p	Tumor	Upregulated	VE-Cad, p120	Increase vascular permeability; Promote the generation and metastasis of CTCs	[30]
miR-25-3p, miR-130b-3p, miR-425-5p, miR-934	Tumor	Upregulated	KLF2, KLF4, PI3K / Akt, PTEN	Angiogenesis; M2 polarization of macrophages	[29, 96, 97]
miR-146a-5p, miR-155-5p	Tumor	Upregulated	SOCS1, ZBTB2	Promote activation of CAFs; Induction of EMT	[22]
miR-181a-5p	Tumor	Upregulated	SOCS3, IL6/STAT3	Activate HSC; PMN formation	[32]
miRNA-106b-5p, miR-106b-3p	Tumor/serum	Upregulated	PDCD4, DLC-1	M2 polarization of macrophages; Accelerated metastasis; Induction of EMT	[12, 98]
miR-135a-5p, miR-25	Tumor	Upregulated	LATS2 /YAP1 / MMP7, SIRT6	PMN formation; Liver metastases	[18, 99]
miR-221-3p, miR-221/222	Tumor/serum	Upregulated	SOCS3, SPINT1	Angiogenesis; Liver metastases; PMN formation	[28, 100]
miR-128-3p	Tumor	Upregulated	FOXO4, TGF-β / SMAD, JAK / STAT3	Induction of EMT	[20]
miR-17-5p	CAF	Upregulated	RUNX3/ MYC / TGF-β1	Accelerated metastasis	[101]
miR-92a-3p	CAF	Upregulated	Wnt / β-catenin, FBXW7, MOAP1	Inhibit mitochondrial apoptosis to promote cell stemness, EMT, metastasis, and 5-FU / OX resistance	[47]
miR-21-5p, miR-155-5p	TAM	Upregulated	BRG1	Promote CRC cell migration and invasion	[102]
miR-1229	Serum	Upregulated	HIPK2	Angiogenesis; Accelerated metastasis	[16]
circPACRGL	Tumor	Upregulated	miR-142-3p, miR-506-3p	Accelerated metastasis; Promotion of N1 to N2 differentiation of neutrophils	[103]
circLONP2	Tumor	Upregulated	DDX1, DGCR8 / Drosha	Accelerated metastasis	[104]
circ-133	plasma	Upregulated	miR-133a / GEF-H1 / RhoA	Accelerated metastasis	[105]
circ-ABCC1	Tumor	Upregulated	Wnt / β-catenin	Accelerated metastasis	[106]
circEIF3K	CAF	Upregulated	miR-214	Accelerated metastasis	[107]
lncRNA RPPH1, lncRNA HLA-F-AS1	Tumor	Upregulated	TUBB3, miR-375	Induction of EMT; M2 polarization of macrophages; Accelerated metastasis	[108, 109]
lncRNA MALAT1	Tumor	Upregulated	miR-26a/26b, FUT4, PI3K / Akt / mTOR	Accelerated metastasis	[110]
HSPC111	Tumor	Upregulated	ACLY	PMN formation; Liver metastasis	[13]
IRF-2	Tumor	Upregulated	VEGFC	To guide tumor metastasis in SLN	[111]
PrPC	Tumor	Upregulated	-	Angiogenesis; Accelerated metastasis	[112]
Gas6, DPP4	Tumor	Upregulated	Axl, Twist1, Smad pathway	Angiogenesis	[113, 114]
b. Inhibit cancer progression
miR-1255b-5p	Tumor	Downregulated	hTERT	Inhibit EMT; Inhibit metastasis	[21]
miR-193a-5p	plasma	Downregulated	CUX1, ITSN1	Inhibit metastasis	[88]
miR-3940-5p	MSC	Upregulated	ITGA6	Inhibit EMT; Inhibit metastasis	[115]
miR-203a-3p	Hepatocyte	–	E-cadherin, Src	Inhibit metastasis	[33]
circRHOBTB3	Tumor	Downregulated	ENO1, ENO2	Inhibition of EMT; Tumor suppressor	[116]
ANGPTL1	Tumor	Downregulated	JAK2 / STAT3	Inhibit liver metastasis; Block vascular leakage	[34]

VE-Cad vascular endothelial cadherin, KLF2 Krüppel-like factor 2, KLF4 Krüppel-like factor 4, PTEN Phosphatase and tensin homolog, SOCS1 suppressor of cytokine signaling 1, ZBTB2 zinc finger and BTB domain containing 2, SOCS3 suppressor of cytokine signaling 3, PDCD4 programmed cell death 4, DLC-1 deleted in liver cancer-1, LATS2 large tumor suppressor kinase 2, YAP1 yes-associated protein 1, SIRT6 sirtuin 6, SPINT1 serine protease inhibitor Kunitz type 1, RUNX3 3'-untranslated regions (UTRs) of RUNX family transcription factor 3, DDX1 DEAD-Box 1, DGCR8 DiGeorge syndrome critical region gene 8, GEF-H1 Rho guanine nucleotide exchange factor, TUBB3 β-III tubulin, FUT4 fucosyltransferase 4, ACLY ATP-citrate lyase, DPP4 dipeptidyl peptidase IV, PrPC prion protein, hTERT human telomerase reverse transcriptase, MSC mesenchymal stem cell, CUX1 CUT-like homeobox 1, ITSN1 intersectin 1, ITGA6 Integrin alpha6, NFs normal fibroblasts, SLN Sentinel lymph nodes

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ISSN: 1477-3155

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