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Published on: May 27, 2016
MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines
Richard Hummel1, Corina Sie1, David I Watson1
1Richard Hummel, Corina Sie, David I Watson, Tingting Wang, Alfiya Ansar, Damian J Hussey, Department of Surgery, Flinders University, Bedford Park, South Australia 5042, Australia.
Aim:
To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines.
Methods:
An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (5-FU) resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction (PCR). The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated.
Results:
Chemotherapy resistant sublines were found to have specific miRNA signatures, and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line, and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent. Amongst others, miR-27b-3p, miR-193b-3p, miR-192-5p, miR-378 a-3p, miR-125a-5p and miR-18a-3p were dysregulated, consistent with negative posttranscriptional control of KRAS, TYMS, ABCC3, CBL-B and ERBB2 expression via these miRNAs.
Conclusion:
The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer.
Insights
MicroRNA (miRNA) signatures differ in esophageal cancer cells resistant to chemotherapy. These specific miRNA profiles may influence treatment outcomes in esophageal adenocarcinoma and squamous cell carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Esophageal cancer exhibits resistance to chemotherapy.
- MicroRNAs (miRNAs) are implicated in cancer development and progression.
- Understanding miRNA roles in chemoresistance is crucial for treatment optimization.
Purpose of the Study:
- To investigate microRNA (miRNA) expression profiles in chemotherapy-resistant esophageal cancer cell lines.
- To identify potential miRNA targets involved in chemoresistance.
- To differentiate miRNA signatures based on cancer subtype and chemotherapeutic agent.
Main Methods:
- Utilized an in-vitro model of acquired chemotherapy resistance in esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) cells.
- Compared miRNA expression profiles using microarray and quantitative real-time polymerase chain reaction (PCR).
- Evaluated the expression of chemotherapy-relevant genes targeted by dysregulated miRNAs.
Main Results:
- Chemotherapy-resistant sublines displayed distinct miRNA signatures.
- Signatures varied between cisplatin- and 5-fluorouracil (5-FU)-resistant cells, and between EAC and ESCC subtypes.
- Dysregulated miRNAs, including miR-27b-3p and miR-192-5p, were linked to the posttranscriptional control of genes like KRAS and ERBB2.
Conclusions:
- MicroRNA expression significantly impacts chemotherapy resistance in esophageal cancer.
- Specific miRNA signatures could serve as biomarkers for predicting treatment response.
- Further research into miRNA-targeted therapies may overcome chemoresistance.
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