Table 1.
The microRNAs involved in GC metastasis, their direct targets and regulated signaling pathways.
| Signal Pathway | MicroRNA | Target | Role in GC Metastasis | Materials | Reference |
|---|---|---|---|---|---|
| Wnt/β-catenin | miR-18a miR-19a |
SMAD2 | Overexpression of miR-18a was associated with lymph node metastasis and the distant metastases development. Overexpression of miR-19a was associated with lymph node metastasis. |
GC tissues | [49] |
| miR-30c-5p | MTA1 | Decreased expression level of miR-30c-5p was associated with lymph nodes metastasis. | GC tissues | [59] | |
| miR-33a | SNAI2 | Overexpression of miR-33a inhibited metastasis and tumor growth in vivo. | GC tissues, cell lines and nude mice | [84] | |
| miR-93 miR-106a |
TIMP2 | Overexpression of miR-106a and miR-93 was associated with lymph node metastasis and vascular invasion. | FFPE samples, cell lines and GC tissues |
[27,64] | |
| miR-140-5p | WNT1 | Decreased expression level of miR-140-5p was associated with lymph nodes metastasis. | GC tissues | [85] | |
| miR-142-5p | CYR61 | Downregulation of miR-142-5p was associated with the metastases development, relapse and poor prognosis. | GC tissues | [86] | |
| miR-143 miR-145 |
MYO6 | miR-143, miR-145 inhibit EMT and metastasis. | GC tissues, cell lines and nude mice | [60] | |
| miR-188-5p | PTEN | Overexpression of miR-188-5p was associated with lymph nodes metastasis and the distant metastases development. | GC tissues | [48] | |
| miR-204 | SNAIL | Decreased expression level of miR-204 was associated with the metastases development. | GC tissues, cell lines and nude mice | [63] | |
| miR-302b miR-520d-3p |
EPHA2 | Downregulation of miR-302b correlated with the depth of tumor invasion, lymph nodes metastasis, and later stage of GC. Downregulation of miR-520d-3p correlated with increased tumor invasion, lymph node metastasis, and clinical stage. |
GC tissues, cell lines and nude mice | [29,30,66] | |
| miR-330-3p | PRRX1 | Negative correlation between expression level of miR-330-3p and tumor size, TNM stage, and the degree of lymph nodes metastasis | GC tissues | [87] | |
| miR-361-5p | Indirectly affects SNAIL, E-cadherin, β-catenin |
Decreased expression level of miR-361-5p correlated with lymph node metastasis and the distant metastases development. | GC tissues, cell lines and nude mice | [88] | |
| miR-516a-3p | SULF1 | Decreased expression level of miR-516a-3p was associated with the spread of metastases in the peritoneum. | Nude mice | [62] | |
| miR-520f-3p | SOX9 | Decreased expression of miR-520f-3p correlated with the depth of tumor invasion, metastases development, and poor prognosis in GC patients. | GC tissues | [89] | |
| miR-1225-5p | IRS1 | Decreased expression level of miR-1225-5p correlated with the depth of tumor invasion, lymph node metastasis, and distant metastases. | GC tissues, cell lines and nude mice | [90] | |
| PI3K/AKT/mTOR | miR-28 | PTEN | MiR-28 knockdown inhibited the proliferative and invasive properties of GC cells. | Cell lines | [71] |
| miR-142-5p | PIK3CA | Overexpression of miR-142-5p inhibited cell proliferation and tumor growth and metastasis. | GC tissues, cell lines and nude mice | [91] | |
| miR-197 | MTDH | Revealed a negative correlation between the expression level of miR-197 and the size of the tumor, the depth of invasion and lymph nodes metastasis. | GC tissues | [72] | |
| miR-340 | SPP1 | Overexpression of miR-340 induced apoptosis, inhibited proliferation, invasion, in vitro migration, and in vivo tumor growth. | Cell lines and nude mice | [67] | |
| miR-379 | FAK | miR-379 was associated with lymph nodes metastasis. | GC tissues | [68] | |
| miR-498 | BMI-1 | Decreased expression level of miR-498 was associated with lymph node metastasis and poor prognosis in GC patients. | GC tissues | [73] | |
| miR-520a-3p | WEE1 | Induced expression of miR-520a-3p decreased tumor size. | Cell lines and nude mice | [69] | |
| miR-1254 | SMURF1 | Decreased expression level of miR-1254 was associated with an increase in tumor size and the degree of lymph nodes metastasis. | GC tissues, cell lines and nude mice | [70] | |
| NF-κB | miR-9 |
D1, ETS1, NF-κB1 |
Decreased expression level of miR-9 was associated with lymph nodes metastasis and the distant metastases development. | GC tissues, cell lines and nude mice | [74,92] |
| miR-216a-3p | RUNX1 | Increased miR-216 expression correlated with lymph node metastasis. | GC tissues | [44] | |
| miR-508-3p | NFKB1 | Overexpression of miR-508-3p inhibited the invasive properties of GC cells in vitro. In addition, miR-508-3p suppressed the level of MMP9 expression. | Cell lines and nude mice | [75] | |
| NF-kB; Wnt/β-catenin | miR-7 | RELA, IGF1R | MiR-7 transfection inhibits distant metastases in vivo. | GC tissues, cell lines and nude mice | [37,38] |
| miR-146a | IRAK1, EGFR | Decreased expression level of miR-146a was associated with lymph node metastases. | GC tissues | [93] | |
| JAK/STAT | miR-216a | JAK2 | Decreased expression level of miR-216 correlated with lymph node metastasis. | GC tissues and cell lines |
[42] |
| NF-κB; JAK/STAT |
miR-1224 | FAK | Decreased expression level of miR-1224 was associated with metastasis to lymph nodes in intestinal type of GC. | GC tissues and FFPE tissues | [58] |
| RHOA-ROCK | miR-31 | RHOA | Decreased expression level of miR-31 was associated with lymph nodes metastasis. It was shown that miR-31 inhibited the development of distant metastases. | GC tissues, cell lines and nude mice | [94] |
| RAS/RAF/EKK/MAPK | miR-302b | CDK2 | Decreased expression level of miR-302b was associated with lymph node metastasis and advanced GC. | GC tissue | [28] |
| miR-585 | MAPK1 | Decreased expression level of miR-585 was associated with tumor invasion, lymph node metastasis, and advanced GC. | GC tissues, cell lines and nude mice | [95] | |
| PI3K/AKT/mTOR; RAS/RAF/EKK/MAPK; JAK/STAT and Notch |
miR-21 miR-25 miR-221/222 miR-374b-5p miR-590-5p |
RECK | Overexpression of these microRNAs was associated with lymph nodes metastasis. | GC tissues and cell lines | [80,81,82,83] |