Table 1.
Summary of ncRNAs that mediate lymphangiogenesis and their targets in different tumor microenvironments, with the specific mechanisms, types of tissues, and discovery platforms applied in reported studies.
| ncRNA Expression | Targets | Disease Model | Mechanism | Type of Tissue | Discovery Platform | Ref. |
|---|---|---|---|---|---|---|
| Anti-lymphangiogenic | ||||||
| ↓miR-27b | ↑leptin, ↑VEGF-C, ↑FAK, ↑PI3K/Akt signaling | Chondrosarcoma | Correlative, direct | Tumor tissue (mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [104] |
| ↑adiponectin, ↑VEGF-C, ↑CAMKII, AMPK, ↑p38 | Chondrosarcoma | Correlative, direct | Tumor tissue (mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [129] | |
| ↑VEGF-C | Gastric cancer | Correlative, indirect | Plasma sample (human), cell lines | miRNA microarray, RT-qPCR | [130] | |
| ↓miR-300 | ↑VEGF-C, ↑WISP, ↑ILK, Akt signaling | OSCC | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [131] |
| ↓miR-381 | ↑VEGF-C, ↑bFGF | Chondrosarcoma | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [132] |
| ↓miR-507 | ↑VEGF-C, ↑CCL5 | Chondrosarcoma | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [133] |
| ↓miR-624-3p | ↑VEGF-C, ↑BDNF, ↑MEK/ERK/mTOR signaling | Chondrosarcoma | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [134] |
| ↓miR-186 | ↑VEGF-C, ↑resistin | Chondrosarcoma | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [103] |
| ↓miR-3178, ↓miR-593-5p, ↓miR-4485, ↓miR-17, ↓miR-469, ↓miR-124-5p | ↑VEGF-C (needs further investigation) | Gastric cancer | Correlative, indirect | Tumor tissue (human), cell lines | RT-qPCR, miRNA microarray, Taqman RT-PCR (validation) | [135] |
| ↓miR-126 | ↑VEGF-A | OSCC | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, IHC, methylation specification PCR | [136] |
| ↓miR-503-5p | ↑VEGF-A, ↑AKT | Colon cancer | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, WB | [108] |
| ↓miR-221, ↓miR-222 |
↑ETS1 ↑ETS2 | Kaposi’s sarcoma | Direct | Cell lines | Luciferase assay, RT-qPCR, miRNA microarray | [137] |
| ↓circNFIB1 | ↑miR-486-5p (sponging)/↑VEGF-C | PDAC | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, NGS, WB, ISH | [138] |
| Pro-lymphangiogenic | ||||||
| ↑miR-128 | ↓VEGF-C, ↓ERK, ↓Akt, ↓p38 | NSCLC | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, WB | [127] |
| ↓VEGF-C | Bladder cancer | Correlative, direct | Tumor, tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, WB | [128] | |
| ↑miR-195-3p | ↓VEGF-C, ↓CCL4, ↓JAK2/STAT3 signaling | OSCC | Correlative, direct | Serum (human), tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [139] |
| ↑miR-206 | ↓VEGF-C, ↓KRAS, ↓NFκB, ↓ANXA2 | PDAC | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC | [140] |
| ↑miR-182-5p | ↓VEGF-C, ↓VEGFA, ↓VEGFR-2, ↓VEGFR-3, ↓ERK, ↓AKT | Colon cancer | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, WB | [141] |
| ↑miR-486-5p | ↓NRP2 | CRC | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [142] |
| ↑miR-93 | ↓ANGPT-2 | MPE | Correlative, direct | Tissue specimens (human), cell lines | Luciferase assay, RT-qPCR, miRNA microarray | [143] |
| ↑miR-129-5p | ↓ZIC2, ↓Hedgehog signaling (Smo, Sli1, Shh) | NPC | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, IHC, gene-based microarray, WB | [144] |
| ↑miR-548k | ↓ADAMTS1, ↑VEGF-C/VEGFR-3 signaling | ESCC | Correlative direct | Tumor tissue (mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [145] |
| ↑miR-19 | ↓THBS1, ↑MMP-9/VEGF-C | Colon cancer | Correlative, direct | Tumor tissue (mouse), cell lines | Luciferase assay, functional assays | [146] |
| ↑miR-648, ↑miR-5002-3p, ↑miR-4485, ↑miR-135a, ↑miR-17, ↑miR-1469, ↑miR-124-5p |
↑VEGFC (needs further investigation) | Gastric cancer | Correlative | Tumor tissue (human), cell lines | RT-qPCR, miRNA microarray, Taqman RT-PCR (validation) | [135] |
| ↑miR-526b, ↑miR-655 |
↓PTEN, ↑PI3K/Akt signaling, ↑VEGF family, ↑COX-2, ↑LYVE-1, ↑EP4 (needs further investigation) | Breast cancer | Correlative | Tumor tissue (human), cell lines | RT-qPCR, WB | [147] |
| ↑miR-155 | ↓BRG1, ↑STAT3/VEGF-C, ↑LYVE-1 | NKTCL | Correlative, direct | Tumor tissue (mouse), cell lines | Luciferase assay, RT-qPCR, IHC, WB | [148] |
| ↑miR-221-3p | ↓VASH-1, ↑ERK/Akt signaling | CSCC | Correlative, direct | Tumor tissue (human), cell lines | Luciferase assay, RT-qPCR, IHC, ISH, WB | [149] |
| ↑miR-31 | ↓FAT4 | Kaposi’s sarcoma | Direct | Cell lines | Luciferase assay, RT-qPCR, miRNA microarray | [137] |
| ↑miR-27a | ↓SMAD4 | Colon cancer | Direct | Cell lines | Luciferase assay, RT-qPCR, miRNA microarray, WB | [150] |
| ↑ANRIL | ↓CDKN2A, ↑VEGFC, ↑VEGFR-3, ↑LYVE-1 | Colon cancer | Correlative, indirect | Tumor tissue (human), cell lines | RT-qPCR, IHC, WB | [90] |
| ↑BLACAT2 | ↑VEGF-C, ↑WDR5 | Bladder cancer | Correlative, direct | Tumor tissue (human, mouse), cell lines | RT-qPCR, NGS, microarray, IHC, ISH, RNA IP, WB, mass spectrometry, ChIRP | [151] |
| ↑HUMT | ↑FOXK1, ↑YBX1, ↑Akt/mTOR/VEGF-C signaling | Breast cancer | Correlative, direct | Tumor tissue (human, mouse), cell lines | RT-qPCR, IHC, ISH, FISH, RNA IP, ChIP, WB | [152] |
| ↑ASLNC07322 | ↓SMAD4, sponging miR-128-3p, ↑VEGF-C | Colon cancer | Correlative, direct | Tumor tissue (human, mouse), cell lines | Luciferase assay, RT-qPCR, ISH, ChIP | [153] |
| ↑HANR | ↓miR-296, ↑EAG1/VEGF-A signaling | HCC | Direct | Cell lines | Luciferase assay, RT-qPCR, WB | [154] |
Correlative: Correlation of expressions between ncRNAs with samples or tissues applied in the study; direct: Indicates direct binding or interaction between ncRNAs and targeted genes; indirect: no direct interaction or binding between ncRNAs and targeted genes reported in the particular study. ncRNA, non-coding RNA; NSCLC, non-small cell lung cancer; OSCC, oral squamous carcinoma cell; PDAC, pancreatic adenocarcinoma cell; CRC, colorectal cancer; MPE, malignant pleural effusion; NKTCL, natural killer/T cell lymphoma; NPC, nasopharyngeal carcinoma; ESCC, esophageal squamous carcinoma cell; CSCC, cervical squamous carcinoma; HCC, hepatocellular carcinoma; RT-qPCR, real-time quantitative polymerase chain reaction; WB, Western blotting; NGS, next gene sequencing; IHC, immunohistochemistry; ISH, in-situ hybridization; FISH, fluorescence in-situ hybridization; ChIRP, chromatin isolation by RNA purification; ChIP, chromatin immunoprecipitation; RNA IP, RNA immunoprecipitation.