Extracellular vesicles circular RNA: A new perspective and clinical application potential for mediating chemoresistance in colorectal cancer

Table 1 Summary of dysregulated circular RNAs in colorectal cancer chemoresistance

Chemotherapy regimen	CircRNAs	Annotated number	Expression	Samples	Targets/regulators	Function	Ref.
Oxaliplatin	Hsa_circ_0079662	-	Up	Cells	Tumour necrosis factor alpha signaling	Promotes proliferation, migration, invasion, and chemoresistance	Lai et al[24]
	Circ-CD44	Hsa_circ_0000291	Up	Tissues; cells	MiR-330-5p/ABCC1	Promotes proliferation, migration, invasion, and chemoresistance	Zhao et al[32]
	Hsa_circ_0071589	-	Up	Cells	MiR-133b	Aggravates stemness and promotes chemoresistance	Lv et al[33]
	Circ_0000395	-	Up	Cells	MiR-153-5p/myosin VI	Promotes proliferation, migration, and chemoresistance	Xiao et al[34]
	Circ_0082182	Has_circ_0082182	Up	Tissues; cells	MiR-326	Promotes chemoresistance	Wang et al[35]
	Circ-PDIA3	Hsa_circ_0002891	Up	Tissues; cells	MiR-449a	Inhibits pyroptosis and promotes chemoresistance	Lin et al[36]
	Circ-SEC24B	Hsa_circ_0001436	Up	Tissues; cells	Sushi repeat-containing protein X-linked 2	Activates autophagy and promotes chemoresistance	Wang et al[37]
	Circ-PDE4D	Hsa_circ_0072568	Up	Cells	Hsa-miR-569	Inhibits chemoresistance	Li et al[38]
	Circ-ZEB1	Hsa_circ_0000229	Up	Tissues	MiR-200c	Promotes chemoresistance	Chen et al[47]
	Circ_0032833	-	Up	Cells	MiR-125-5p	Promotes chemoresistance	Li et al[48]
	Hsa_circ_0000338	-	Up	Cells	-	Inhibits chemoresistance	Hon et al[49]
5-fluorouracil	Hsa_circ_0002813	-	Up	Cells	MiR-541-3p	Promotes chemoresistance	Cheng et al[39]
	Hsa_circ_0000236	-	Up	Cells	MiR-4769-5p	Promotes chemoresistance
	Circ_0007031	-	Up	Cells	MiR-133b/ABCC5	Promotes chemoresistance	He et al[40]
	Has_circ_0055625	-	Up	Serum	-	Promotes chemoresistance	Liu et al[41]
	Circ_0014130	Hsa_circ_0014130	Up	Tissues; cells	MiR-197-3p/6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3	Promotes chemoresistance	Wang et al[42]
	Circ_0004585	-	Up	Tissues; cells	MiR-874-3p/cyclin D1	Promotes chemoresistance	Wang et al[43]
	Circ-PRKDC	Circ_0136666	Up	Tissues; cells	MiR-375/forkhead box protein M1	Promotes chemoresistance	Chen et al[44]
	Circ-ERBB2	Hsa_circ_0043459	Up	Cells	MiR-181a-5p/phosphatase and tensin homologue deleted on chromosome 10/AKT	Promotes chemoresistance	Zhang et al[45]
	Hsa_circ_0007031	-	Up	Cells	MiR-885-3p/AKT3	Promotes chemoresistance
	Hsa_circ_0000504	-	Up	Cells	MiR-485-5p/signal transducer and activator of transcription 3/AKT3	Promotes chemoresistance	Xiong et al[46]
	Hsa_circ_0048234	-	Down	Cells	MiR-671-5p/epidermal growth factor receptor	Promotes chemoresistance
	Circ-ZEB1	Hsa_circ_0000229	Up	Tissues	MiR-200c	Promotes chemoresistance	Chen et al[47]
	Circ_0032833	-	Up	Cells	MiR-125-5p	Promotes chemoresistance	Li et al[48]
	Hsa_circ_0000338	-	Up	Cells	-	Inhibits chemoresistance	Hon et al[49]
Cetuximab	Circ-IFNGR2	Hsa_circ_001185	Up	Cells	MiR-30b	Promotes chemoresistance	Zhang et al[50]
		Hsa_circ_000339	Up	Cells	MiR-30b	Promotes chemoresistance
	Circular hypoxia inducible factor 1 subunit alpha	Hsa_circ_0007976	Up	Cells	MiR-361-5p	Affects cellular aerobic metabolism, glycolysis levels, and promotes chemoresistance	Geng et al[51]
Irinotecan	Hsa_circ_001680	-	Up	Tissues; cells	MiR-340	Promotes proliferation, migration, and chemoresistance	Jian et al[52]
Cisplatin	CircRNA_101277	-	Up	Tissues; cells	MiR-370/interleukin-6	Promotes chemoresistance	Lv et al[53]

ABCC: Adenosine triphosphate binding cassette subfamily C; AKT: Protein kinase B; CircRNA: Circular RNA; ZEB1: Zinc finger E-box binding homeobox 1.

Table 2 List of extracellular vesicles-circular RNAs involved in colorectal cancer chemoresistance or chemosensitivity

	EV content	Expression	EV source	Targets/regulators	Function	Drug	Ref.
Chemosensitivity	Circ-FBXW7	Down	Human fetal colon cell culture	MiR-18b-5p	Increases apoptosis, inhibits epithelial-mesenchymal transition, and improves chemosensitivity	OXA	Xu et al[58]
	Circ_0094343	Down	Cell lines (NCM460 and HCT116)	MiR-766-5p/tripartite motif-containing 67	Inhibits the proliferation, clone formation, glycolysis of colorectal cancer cells, and improves chemosensitivity	5-FU, OXA, and DOX	Li et al[59]
Chemoresistance	Circ_0067557	Up	CAFs	Lin28A, Lin28B	Promotes proliferation, migration, invasion, and chemoresistance	5-FU, OXA	Yang et al[25]
	Hsa_circ_0000338	Up	HCT116-R	-	Promotes chemoresistance	5-FU, OXA	Hon et al[49]
	Hsa_circ_0004085	Up	Fusobacterium nucleatum-infected colon cancer cells	GRP78, ATF6p50	Relieves endoplasmic reticulum stress in recipient cells and promotes chemoresistance	5-FU, OXA	Hui et al[60]
	Circ_0000338	Up	Cell lines (SW480/5-FU and HCT116/5-FU)	MiR-217, miR-485-3p	Promotes chemoresistance	5-FU	Zhao et al[61]
	Cric-N4BP2 L2	Up	CAFs	Eukaryotic translation initiation factor 4A3/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin	Aggravates stemness and promotes chemoresistance	OXA	Qu et al[62]
	Hsa_circ_0005963	Up	Serum and cell lines (SW480, HCT116, and HEK293)	MiR-122/pyruvate kinase muscle isozyme M2	Promotes glycolysis and chemoresistance	OXA	Wang et al[63]
	Circ_0001610	Up	Cell lines (DLD1 and HCT15)	MiR-30e-5p	Increases oxidative phosphorylation activity and stemness phenotype in recipient cells leading to chemoresistance	OXA	Deng et al[64]
	Has_circ_0004771	Up	Serum and cell lines (NCM460, SW620, and HCT116)	MiR-653/ZEB2	Promotes chemoresistance	5-FU	Qiao et al[65]
	Circ_0006174	Up	Cell lines (LoVo/DOX, and HCT116/DOX)	MiR-1205/cyclin D2	Promotes chemoresistance	DOX	Zhang et al[66]

CAFs: Cancer-associated fibroblasts; CircRNA: Circular RNA; DOX: Doxorubicin; EV: Extracellular vesicle; OXA: Oxaliplatin; 5-FU: 5-fluorouracil.