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The Role of UCHL3 in Malignant Melanoma

Nabiyar, Elena (2021) MOBN03 20201
Degree Projects in Molecular Biology
Popular Abstract
The Role of UCHL3 in Malignant Melanoma

Malignant melanoma is the deadliest types of skin cancer that originates from skin pigment (melanin) producing cells named melanocytes. It is known that ultraviolet (UV) radiation is one of the major sources for causing melanoma via damaging the cellular machinery. During the process of primary tumor progression into the metastatic form, a series of molecular and structural changes might happen. Among all these changes, modifications of cellular proteins which is collectively known as posttranslational modification (PTM) play major roles in cancer metastasis. Ubiquitination is one type of PTM where small protein called ubiquitin is coupled to a given cellular protein that leads to the change in... (More)
The Role of UCHL3 in Malignant Melanoma

Malignant melanoma is the deadliest types of skin cancer that originates from skin pigment (melanin) producing cells named melanocytes. It is known that ultraviolet (UV) radiation is one of the major sources for causing melanoma via damaging the cellular machinery. During the process of primary tumor progression into the metastatic form, a series of molecular and structural changes might happen. Among all these changes, modifications of cellular proteins which is collectively known as posttranslational modification (PTM) play major roles in cancer metastasis. Ubiquitination is one type of PTM where small protein called ubiquitin is coupled to a given cellular protein that leads to the change in the property of the modified protein functions. Interestingly, our cellular machinery has a mechanism to regulate this ubiquitination process through the removal of the added Ubiquitin (deubiqitination) via Deubiquitinating enzymes (DUBs). DUBs are known to be involved in the various cellular functions and proven to be implicated in the regulation of tumor progression. One of DUBs enzymes is Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) which has dual roles in ubiquitination/deubiqitination and neddylation of intracellular proteins.

In the present project, the role of UCHL3 enzyme was investigated in primary and metastatic human and murine melanoma cell lines. To start with, the expression of UCHL3 at the protein level was determined in the cell lines using Western blotting techniques. The results from Western blotting demonstrated that the expression level of UCHL3 in metastatic melanoma cell line is highly upregulated in comparison to the primary cell line. Also, the functional role of UCHL3 in proliferation, wound healing and invasion was investigated using these different primary and metastatic cell lines. The level of cell migration and invasion was shown to be enhanced in melanoma cell lines with higher expression of UCHL3 though no effect in cell proliferation. The impact of UCHL3 in promoting tumor metastasis was investigated in experimental mouse models using murine melanoma cell line (B16F10) after modifying the level of UCHL3 (UCHL3-high/B16F10 sh-ctrl and UCHL3-low /B16F10 sh-UCHL3). Results from the mouse experiment revealed that mice engrafted with UCHL3-high cell line (B16F10 sh-ctrl) displayed lung metastasis unlike UCHL3-low (B16F10 sh-UCHL3).

In conclusion, increased level of UCHL3 expression could have an important role in promoting cell migration and invasion which are essential features of malignant melanoma.


Master’s Degree Project in Molecular Biology, 60 credits, 2021
Department of Biology, Lund University

Advisor: Ramin Massoumi
Advisors department: Translational Cancer Research (TCR), Lund University (Less)
Please use this url to cite or link to this publication:
author
Nabiyar, Elena
supervisor
organization
course
MOBN03 20201
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9043309
date added to LUP
2021-04-23 15:35:03
date last changed
2021-04-23 15:35:03
@misc{9043309,
  author       = {{Nabiyar, Elena}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The Role of UCHL3 in Malignant Melanoma}},
  year         = {{2021}},
}