Therapeutic applications of miRNAs in FLT3+ Acute Myeloid Leukemia: Role of miRNA-155
(2023) MOBN03 20231Degree Projects in Molecular Biology
- Abstract
- The Fms-like tyrosine kinase 3 (FLT3) mutation, especially FLT3- internal tandem duplications (FLT3-ITD), is common in AML and associated with poor prognosis and resistance to therapy. This study explores an alternative approach by investigating the role of MicroRNA-155 (miR-155) in AML, known for its oncogenic properties. Previous research has linked miR-155 to poor AML prognosis, particularly in FLT3-ITD cases. The project aims to understand the relationship between miR-155 and FLT3, specifically how miR-155 regulates FLT3 protein. Using the MV4-11 leukemic cell line (FLT3-ITD) and THP-1 cell line (WT-FLT3), we knocked down miR-155 and analyzed its effect through protein expression, apoptosis, colony formation, and proliferation assays... (More)
- The Fms-like tyrosine kinase 3 (FLT3) mutation, especially FLT3- internal tandem duplications (FLT3-ITD), is common in AML and associated with poor prognosis and resistance to therapy. This study explores an alternative approach by investigating the role of MicroRNA-155 (miR-155) in AML, known for its oncogenic properties. Previous research has linked miR-155 to poor AML prognosis, particularly in FLT3-ITD cases. The project aims to understand the relationship between miR-155 and FLT3, specifically how miR-155 regulates FLT3 protein. Using the MV4-11 leukemic cell line (FLT3-ITD) and THP-1 cell line (WT-FLT3), we knocked down miR-155 and analyzed its effect through protein expression, apoptosis, colony formation, and proliferation assays for functional validation. The data obtained suggest there is a positive correlation between miR-155 and FLT3 as both expressions decreased as a result from treatment with antimiR-155. The functional studies also demonstrated a positive correlation as the proliferation showed a significant decrease followed by a recovery at 48h implying effects of cancer adaptability. Inducing apoptosis further demonstrated a positive correlation as the rate increased. The colony formation assay showed a reduction in colony numbers over 7 days. This research seeks insights into potential treatments targeting miR-155 in AML, addressing the challenges caused by FLT3 mutations and enhancing treatment efficacy. (Less)
- Popular Abstract
- miRNA-155 Therapy for Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a blood cancer characterized by abnormal changes in genes and their control switches. This results in abnormal cell growth and survival of immature myeloid cells. FLT3 is a protein which plays a central role in the process of blood cell formation, and mutations in the FLT3 gene have been found and characterized in 25-30% of all AML patients. Patients suffering from AML are linked to poor prognosis and a low survivability due to its ability to develop resistance to treatments and disease relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that help regulate gene expression. In AML, miR-155 is a microRNA that plays a central role in the development... (More) - miRNA-155 Therapy for Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a blood cancer characterized by abnormal changes in genes and their control switches. This results in abnormal cell growth and survival of immature myeloid cells. FLT3 is a protein which plays a central role in the process of blood cell formation, and mutations in the FLT3 gene have been found and characterized in 25-30% of all AML patients. Patients suffering from AML are linked to poor prognosis and a low survivability due to its ability to develop resistance to treatments and disease relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that help regulate gene expression. In AML, miR-155 is a microRNA that plays a central role in the development of leukemia. Just like FLT3, miR-155 displayed higher expression in patients diagnosed with AML. The interaction between FLT3 and miR-155 is not fully understood, so in this study we aim to investigate the role of miR-155 in regulating the FLT3 protein.
In this project, we transfect MV4-11 leukemic cells, these are cells containing a mutation in the FLT3 gene readily found in AML patients. By treating them with antimiR-155 and negative control anitmiR-155, we can study the expression and relationship between miR-155 and FLT3. We then preform various functional studies like apoptosis, proliferation, and colony formation assays to validate the effect of their binding.
miRNA as possible targets for novel treatments?
After knocking down miR-155, from the acquired data we can see a positive correlation between miR-155 and FLT3. The data showed a decrease in expression for both miR-155 and FLT3 in antimir-155 treated cells. Thus, impacting cell proliferation, apoptosis, and colony formation. Proliferation was found to be decreased within 24h while Apoptosis increased, and colony formation decreased.
This project aimed to explore the impact of miR-155 on FLT3 regulation, and the results revealed a positive correlation between the two. This suggests that targeting miR-155 could be a promising treatment for Acute Myeloid Leukemia (AML). Since the project is in its early stages, more research is needed to solidify these results. Future studies will involve validating the binding site on FLT3 mRNA for a more comprehensive understanding.
Master’s Degree Project in Molecular Biology MOBN03 60 credits 2023
Department of Biology, Lund University
Advisor: Amr Al Haidari
Clinical Sciences Department, Division of Pathology, Lund University, BMC13, Lund (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9145291
- author
- Truong, Antony
- supervisor
-
- Amr Al-Haidari LU
- Mats Ehinger LU
- organization
- course
- MOBN03 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9145291
- date added to LUP
- 2024-01-16 14:49:52
- date last changed
- 2024-01-16 14:49:52
@misc{9145291,
abstract = {{The Fms-like tyrosine kinase 3 (FLT3) mutation, especially FLT3- internal tandem duplications (FLT3-ITD), is common in AML and associated with poor prognosis and resistance to therapy. This study explores an alternative approach by investigating the role of MicroRNA-155 (miR-155) in AML, known for its oncogenic properties. Previous research has linked miR-155 to poor AML prognosis, particularly in FLT3-ITD cases. The project aims to understand the relationship between miR-155 and FLT3, specifically how miR-155 regulates FLT3 protein. Using the MV4-11 leukemic cell line (FLT3-ITD) and THP-1 cell line (WT-FLT3), we knocked down miR-155 and analyzed its effect through protein expression, apoptosis, colony formation, and proliferation assays for functional validation. The data obtained suggest there is a positive correlation between miR-155 and FLT3 as both expressions decreased as a result from treatment with antimiR-155. The functional studies also demonstrated a positive correlation as the proliferation showed a significant decrease followed by a recovery at 48h implying effects of cancer adaptability. Inducing apoptosis further demonstrated a positive correlation as the rate increased. The colony formation assay showed a reduction in colony numbers over 7 days. This research seeks insights into potential treatments targeting miR-155 in AML, addressing the challenges caused by FLT3 mutations and enhancing treatment efficacy.}},
author = {{Truong, Antony}},
language = {{eng}},
note = {{Student Paper}},
title = {{Therapeutic applications of miRNAs in FLT3+ Acute Myeloid Leukemia: Role of miRNA-155}},
year = {{2023}},
}