- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- Zinc depletion-induced apoptosis is associated with...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
Zinc depletion-induced apoptosis is associated with altered microRNA expression in human breast cancer MDA-MB-231 cells Bakker, Melinda
Abstract
Zinc is an essential trace element required for many physiological functions, including growth. At the cellular level, zinc is required for structural and catalytic roles in thousands of proteins, and adequate labile zinc is an important determinant of cellular viability. However, abnormal zinc accumulation in breast tissue is associated with breast cancer, suggesting that zinc status plays a role in breast cancer pathogenesis. Chelationinduced depletion of labile intracellular zinc promotes apoptosis, or programmed cell death, in multiple breast cancer cell lines. The mechanisms whereby zinc regulates apoptosis remain unclear. In particular, little is known about the role of microRNAs (miRs), a novel class of short non-coding RNA, involved in the regulation of gene expression. Zinc status can influence miR expression, and possibly the processing and stability of miRs. The hypothesis of my thesis research is that miRs are involved in zinc depletion-induced apoptosis in human breast cancer cells. The overall objective of this study was to determine the involvement of miRs in zinc depletion-induced apoptosis in breast cancer MDA-MB-231 cells. Zinc depletion for 24, 48 and 72 h induced apoptosis in 4.5, 24.4 and 28.0 % of the cells, respectively, indicating a time-dependent increase in zinc depletion-induced apoptosis. Expression of 8, 90, and 94 miRs were significantly altered during the early stages of zinc depletion-induced apoptosis, at 3, 12, and 24 h of zinc depletion, respectively. Overall, expression of 285 unique miRs was significantly affected by zinc depletion, duration of zinc depletion, and their interactions. qRT-PCR analysis confirmed that zinc depletion resulted in an increased abundance of miR-132-3p, miR-1246, miR-1273, miR-4484 and miR-4787-5p and a decreased abundance of miR-4521 in a time-dependent manner. MiR-132-3p and miR 1246 have previously been shown to play a role in mediating apoptosis in prostate cancer PC-3 and lung cancer A549 cells, respectively. In conclusion, abundance of numerous miRs was altered during the early stages of zinc depletion-induced apoptosis, indicating possible involvement of these miRs in mediating zinc depletion-induced apoptosis. The role and targets of these miRs in zinc depletion-induced apoptosis requires validation in further research.
Item Metadata
Title |
Zinc depletion-induced apoptosis is associated with altered microRNA expression in human breast cancer MDA-MB-231 cells
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2013
|
Description |
Zinc is an essential trace element required for many physiological functions,
including growth. At the cellular level, zinc is required for structural and catalytic roles in
thousands of proteins, and adequate labile zinc is an important determinant of cellular
viability. However, abnormal zinc accumulation in breast tissue is associated with breast
cancer, suggesting that zinc status plays a role in breast cancer pathogenesis. Chelationinduced
depletion of labile intracellular zinc promotes apoptosis, or programmed cell death,
in multiple breast cancer cell lines. The mechanisms whereby zinc regulates apoptosis
remain unclear. In particular, little is known about the role of microRNAs (miRs), a novel
class of short non-coding RNA, involved in the regulation of gene expression. Zinc status
can influence miR expression, and possibly the processing and stability of miRs. The
hypothesis of my thesis research is that miRs are involved in zinc depletion-induced
apoptosis in human breast cancer cells. The overall objective of this study was to determine
the involvement of miRs in zinc depletion-induced apoptosis in breast cancer MDA-MB-231
cells. Zinc depletion for 24, 48 and 72 h induced apoptosis in 4.5, 24.4 and 28.0 % of the
cells, respectively, indicating a time-dependent increase in zinc depletion-induced apoptosis.
Expression of 8, 90, and 94 miRs were significantly altered during the early stages of zinc
depletion-induced apoptosis, at 3, 12, and 24 h of zinc depletion, respectively. Overall,
expression of 285 unique miRs was significantly affected by zinc depletion, duration of zinc
depletion, and their interactions. qRT-PCR analysis confirmed that zinc depletion resulted in
an increased abundance of miR-132-3p, miR-1246, miR-1273, miR-4484 and miR-4787-5p
and a decreased abundance of miR-4521 in a time-dependent manner. MiR-132-3p and miR 1246 have previously been shown to play a role in mediating apoptosis in prostate cancer
PC-3 and lung cancer A549 cells, respectively. In conclusion, abundance of numerous miRs
was altered during the early stages of zinc depletion-induced apoptosis, indicating possible
involvement of these miRs in mediating zinc depletion-induced apoptosis. The role and
targets of these miRs in zinc depletion-induced apoptosis requires validation in further
research.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2015-04-30
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0165628
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2013-11
|
Campus | |
Scholarly Level |
Graduate
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International