Current Advances in Basic and Translational Research of Cholangiocarcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Current Advances in Basic CCA Research
2.1. Whole-Genome Screening
2.2. Animal Models
2.3. In Vitro Models
2.4. Biomarkers
3. Emerging Roles of Gut Microbiota in CCA
4. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviation
References
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Mouse Model | Recombination | Induced Alterations |
---|---|---|
KrasG12D mice [37] | Alb-Cre | KRAS activation |
KrasG12D;p53L/L mice [37] | Alb-Cre | KRAS activation and p53 deletion |
Smad4Co/CoPtenCo/Co mice [38] | Alb-Cre | Deletion of SMAD4 and PTEN |
Ptenf/fGrp94f/f mice [39] | Alb-Cre | Deletion of PTEN and GRP94 |
AKT/YAP Sleeping Beauty [41] | Sleeping Beauty transposon | Activation of AKT and YAP |
KrasG12D mice with DDC diet [43] | Opn-Cre | KRAS activation and biliary damage |
KrasG12D/CDH1ΔL mice with high fat diet [45] | Alb-Cre | KRAS activation, deletion of E-cadherin, and non-alcoholic fatty liver disease |
Model | Pros | Cons |
---|---|---|
Carcinogen administration (TAA, DEN) | Established, reproducible, and easy procedures Allows to compare early stage and late stage | Long time administration to generate tumors Procedures established mainly for rats Does not mimic human conditions |
Genetically engineered mouse | Mimics common genetic aberrations found in humans Allows to compare early stage and late stage | Double or triple knockout required to generate tumors Does not mimic CCA development associated with biliary damage and inflammation |
Combination of genetically engineered mouse and special feeding | Only single or double knockout or mutation required Mimics biliary damage and inflammation by feeding | Limited previous studies Need to evaluate established tumors as CCA Relatively long period required to establish tumors |
Xenograft mouse | Relatively easy procedures Established methodologies for mice Fast tumor formation | Mismatch species Lack of tumor microenvironment Cannot compare early stage and late stage |
Patient-derived xenograft mouse | Maintains individual CCA characteristics Allows drug testing or genetic screening personalized for the donor patient | Mismatch species Need to maintain mice with tumors for each donor patient |
Syngeneic CCA mouse | Matched species Mimics tumor microenvironment | Relatively challenging procedures Does not mimic CCA development associated with biliary damage and inflammation Cannot compare early stage and late stage |
miRNAs | Samples Analyzed | Expression in CCA | Targets | Association with Poor Survival |
---|---|---|---|---|
miR-22 [31] | CCA tumor | Downregulated | N/A | High expression |
miR-551b [31] | CCA tumor | Downregulated | N/A | Low expression |
miR-200 family [74] | Serum EV | Upregulated | N/A | High levels |
miR-3913 [83] | CCA tumor | Upregulated | N/A | High expression |
miR-29b [84] | CCA tumor | Downregulated | DNMT3B | Low expression |
miR-150 [85] | Serum | Downregulated | N/A | N/A |
miR-144 [86] | CCA tumor | Downregulated | ST8SIA4 | N/A |
miR-451a [86] | CCA tumor | Downregulated | ST8SIA4 | N/A |
miR-1182 [87] | CCA tumor | Downregulated | NUAK1 | N/A |
let-7a [87] | CCA tumor | Downregulated | NUAK1 | N/A |
lncRNAs | Samples Analyzed | Expression in CCA | Primary Targets | Secondary Targets |
---|---|---|---|---|
FOXD2-AS1 [90] | CCA tissues and cells | Upregulated | miR-760 | E2F3 |
GAS5 [91] | CCA tissues and cells | Upregulated | miR-1297 | N/A |
TTN-AS1 [92] | CCA tissues and cells | Upregulated | miR-320a | NRP-1 |
PAICC [93] | CCA tissues and cells | Upregulated | miR-141-3p, miR-27a-3p | YAP1 |
SNHG16 [94] | CCA tissues and cells | Upregulated | miR-146a | GATA6 |
MT1JP [95] | CCA tissues and cells | Downregulated | miR-18a | FBP1 |
CASC2 [96] | CCA tissues and cells | Downregulated | miR-18a | SOCS5 |
HOTAIR [97] | CCA tissues and cells | Upregulated | miR-204 | HMGB1 |
circRNA | Samples Analyzed | Expression in CCA | Primary Targets | Secondary Targets |
---|---|---|---|---|
circ-LAMP1 [98] | CCA tissues and cells | Upregulated | miR-556, miR-567 | YY1 |
circ-CCAC1 [99] | CCA tissues and cells, bile EVs | Upregulated | miR-514a | YY1 |
circ-DNM3OS [100] | CCA tissues and cells | Upregulated | miR-145 | MORC2 |
circ-HIPK3 [101] | CCA tissues and cells | Upregulated | miR-148a-3p | ULK1 |
circ-0000284 [102] | CCA tissues and cells | Upregulated | miR-637 | LY6E |
circ-0005230 [103] | CCA tissues and cells | Upregulated | miR-1238, miR-1299 | N/A |
circ-SMARCA5 [104] | CCA tissues | Downregulated | N/A | N/A |
circ-0000673 [105] | CCA tissues | Upregulated | miR-548b-3p | Various genes predicted |
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Sato, K.; Baiocchi, L.; Kennedy, L.; Zhang, W.; Ekser, B.; Glaser, S.; Francis, H.; Alpini, G. Current Advances in Basic and Translational Research of Cholangiocarcinoma. Cancers 2021, 13, 3307. https://doi.org/10.3390/cancers13133307
Sato K, Baiocchi L, Kennedy L, Zhang W, Ekser B, Glaser S, Francis H, Alpini G. Current Advances in Basic and Translational Research of Cholangiocarcinoma. Cancers. 2021; 13(13):3307. https://doi.org/10.3390/cancers13133307
Chicago/Turabian StyleSato, Keisaku, Leonardo Baiocchi, Lindsey Kennedy, Wenjun Zhang, Burcin Ekser, Shannon Glaser, Heather Francis, and Gianfranco Alpini. 2021. "Current Advances in Basic and Translational Research of Cholangiocarcinoma" Cancers 13, no. 13: 3307. https://doi.org/10.3390/cancers13133307