Table 2 Potential therapeutic targets for CRLM

Non-coding RNA

circNSUN2

Up

CircNSUN2/HMGA2/CXCR4

Forms the circNSUN2/IGF2BP2/HMGA2 RNA–protein ternary complex

Enhances the stability of HMGA2 mRNA to promote CRC cell aggressiveness

[60]

miR-424

Down

Specifically targets FGFR1 to inhibit its expression

[71]

miR-30b

Up

PDGFRB inhibits miR-30b expression

[72]

circPPP1R12A

Up

Hippo-YAP signaling pathway

CircPPP1R12A encodes a functional protein circPPP1R12A-73aa that activates the Hippo-YAP signaling pathway

Promotes the proliferation, migration, and invasion of colon cancer cells

[62]

miR-934

Up

miR-934 downregulates PTEN expression and activates PI3K/AKT signaling pathway in TAMs

Induces polarization of M2 macrophages, polarized M2 releases CXCL13 to activate the CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in metastatic CRC cells

Forms an inflammatory microenvironment to foster CRLM

[27]

miR-92a-3p

Up

Wnt/β-catenin signaling pathway

miR-92a-3p targets FBXW7 and MOAP1, suppressing their expression

Enhances stemness, EMT, and metastasis of CRC cells

[98]

LncRNA UICLM

Up

UICLM down-regulates ZEB2 expression

Promotes liver metastasis of CRC cells

[137]

Chromosome

chromosome 5

Amplification

Upregulates MMPs, promotes the EMT and invasion of colon cancer cells

[52]

Protein

S1PR1

Up

S1PR1–STAT3–IL-6–MDSCs axis

The mutual activation loop between S1PR1 and STAT3 increases IL-6 expression and recruits MDSCs into liver pre-niches

Promotes the proliferation, migration, and invasion

[10]

c-met

Up

c-met activation triggers a series of signaling cascades

Promotes the proliferation and prevents the apoptosis

[61]

FBX8

Up

FBX8 degrades HIF-1α, CDK4, and C-myc

Inhibits cell cycle progression, proliferation, angiogenesis, and metastasis

[90]

CXCR4

Up

The CXCL12/CXCR4 axis activates CRC cells to promote the secretion of exosomal miR-25-3p, miR-130b-3p, and miR-425-5p, which are delivered to TAMs to induce M2 differentiation of TAMs

M2 macrophages cause immune suppression of the microenvironment

Enables CRC cells to escape immune surveillance

[99]

Binding oligomerization domain 1 (NOD1) receptor

Up

p38 MAPK signaling pathway

C12-mediated NOD1 activation interacts with tumor cells and collagens and fibronectins of ECM

Increases ECM adhesion and migration

[101]

transcriptional repressor GFI1

Down

GFI1-STAT3- EP2 signaling pathway in CRC cells

Down-regulated GFI1 increases fibronectin, and vimentin, decrease E-cadherin

Inhibits the EMT, migration, and invasion

[102]

METTL14

Up

METTL1 inhibits the expression of lncRNA XIST

Inhibits the proliferation and invasion of colorectal cancer cells

[121]

Cell type

Lgr5 + CSC

Self-renew, asymmetrical division

Drives metastasis initiation

[81]

Lgr5- CSC

Replenishes the damaged CSC pool

Promotes dissemination, cell escape, metastasis colonization

[81]

CD44v6 + CSC

OPN,TGF-β and SDF-1 produced by CAFs activate CD44v6 + CSC via Wnt/β-catenin pathway in CD44v6 + CSCs

Self-renewal

Promotes migration and metastasis colonization

[82]

BMI-1 + CSC

Autophagy-lysosome pathway in BMI-1 + CSCs

Self-renewal

Promotes proliferation and metastasis

[86]

CXCR2 + MDSC

CXCL1–-CXCR2–-MDSCs axis

CXCL1 in the pre-metastatic liver recruits CXCR2-expressing MDSCs into the pre-metastatic liver

Promotes cancer cell survival, metastatic tumor formation, and growth

[28]

Endoglin-expressing CAFs

TGF-β/BMP signaling pathway in CAFs

interacts with tumor cells

Promotes CAFs invasion and colonization

[96]

CCR2 + CD11b/ Gr1 mid myeloid cells

CCL2 mediates CCR2 + inflammatory monocytes differentiate into immunosuppressive TAMs (CD115 + , CD14 + , CD68 +)

Promotes cancer cells extravasation and growth

[105]

MRC1 + CCL18 + M2-like macrophages

Organ-specifically distributed in the liver exhibits a metabolically high-energy phenotype and is sensitive to adjuvant therapy

Induces suppressive immune microenvironment to promote cancer cells growth and metastasis

[120]