scholarly journals Identifying the key genes and microRNAs in colorectal cancer liver metastasis by bioinformatics analysis and in�vitro experiments

2018 ◽  
Author(s):  
Tao Zhang ◽  
Jianrong Guo ◽  
Jian Gu ◽  
Zheng Wang ◽  
Guobin Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Bioinformatics Analysis ◽  
In Vitro Experiments ◽  
Colorectal Cancer Liver Metastasis ◽  
Key Genes

scholarly journals LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit

Oncogene ◽  
2021 ◽  
Author(s):  
Senlin Zhao ◽  
Bingjie Guan ◽  
Yushuai Mi ◽  
Debing Shi ◽  
Ping Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Metastatic Tumor ◽  
Feedback Circuit ◽  
Colorectal Cancer Liver Metastasis ◽  
Positive Feedback Circuit

AbstractGlycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.

A precision medicine strategy to identify the FGFR pathway as a novel target in colorectal cancer liver metastasis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 660-660
Author(s):  
Erdem Altunel ◽  
Jason Somarelli ◽  
So Young Kim ◽  
Wayne Glover ◽  
Gabrielle Rupprecht ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Precision Medicine ◽  
Cell Lines ◽  
High Throughput ◽  
Therapeutic Targets ◽  
Drug Screen ◽  
Colorectal Cancer Liver Metastasis

660 Background: Colorectal cancer liver metastasis (CRCLM) continues to be a major health problem and despite extensive efforts to develop new drugs, median survival remains at a mere 30 months. The purpose of our study is 1. Develop a precision medicine strategy for patients with CRCLM and 2. Discover novel pathways and treatments to improve outcomes. Methods: In order to develop a precision medicine strategy, 6 matched patient derived xenografts (PDX) and cell lines were established from patients undergoing resection of their CRCLM. A high-throughput drug screen containing over 100 FDA approved drugs was first used in vitro on 3 cell lines to identify therapeutic targets. The top therapeutic targets were validated in vivo. RNA seq was then performed to identify potential predictive markers of response. Results: Our high-throughput drug screen performed on 3 early passage CRC cell lines (CRC057, CRC119 and CRC240) identified ponatinib, a multi TKI, as the only agent to inhibit all 3 cell lines. Subsequent growth inhibition analysis identified the fibroblast growth factor receptor (FGFR) as the main target of ponatinib. In vitro findings were confirmed in vivo in matched PDXs. Western blot analysis post treatment showed evidence of decreased phospho-FGFRs. Further analysis of the main downstream signaling pathways of FGFR (RAS/PI3K/AKT, RAS/MEK/ERK and STAT) demonstrated that the STAT pathway was effectively targeted in all 3 cell lines. In contrast, the ERK pathway was targeted in CRC240 and CRC057 while the p-AKT was targeted in CRC119. Finally, RNAseq revealed different isoforms and mutations in these samples. Conclusions: We have developed a precision medicine strategy for patients with CRCLM using matched cell lines and PDXs coupled with high throughput drug screens and genomic analysis to identify novel targets and specifically identified the FGFR/STAT axis as a therapeutic target. Furthermore, co-targeting FGFR and its downstream pathways may provide synergy and lead to combinatorial therapies that can improve patient outcomes. Finally, RNAseq data can be used to develop predictive markers of therapy.

Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis

2003 ◽  
Vol 90 (12) ◽  
pp. 1556-1564 ◽  
Author(s):  
E. T. Waas ◽  
T. Wobbes ◽  
R. M. L. M. Lomme ◽  
J. DeGroot ◽  
T. Ruers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Colorectal Cancer Liver Metastasis

scholarly journals A comprehensive look at the role of hyperlipidemia in promoting colorectal cancer liver metastasis

2018 ◽  
Vol 9 (16) ◽  
pp. 2981-2986 ◽  
Author(s):  
Yimin Shen ◽  
Caihua Wang ◽  
Yuezhong Ren ◽  
Jun Ye
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Colorectal Cancer Liver Metastasis

Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis

2018 ◽  
Vol 26 (2) ◽  
pp. 593-603 ◽  
Author(s):  
Masanori Oshi ◽  
Georgios Antonios Margonis ◽  
Yu Sawada ◽  
Nikolaos Andreatos ◽  
Jin He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Tumor Burden ◽  
Margin Status ◽  
Negative Margin ◽  
Colorectal Cancer Liver Metastasis
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