Advanced

Small non-coding RNAs in cancer

Persson, Helena LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2009:106.
Abstract
The complex genetics of cancer, which allows tumours to grow and spread while bypassing the control circuitry of the cell, involves dysregulation of the genome, transcriptome and proteome. The importance of protein-coding genes such as growth factors and hormone receptors is well established. Recently, non-coding RNAs have emerged as important players in tumour development with potential to be explored as biomarkers and therapeutic targets. The aim of this thesis was to study the impact of small non-coding RNAs in cancer. MicroRNAs (miRNAs) are one of several types of ~20-30 nucleotide regulatory small non-coding RNAs. They regulate gene expression post-transcriptionally by base pairing to complementary sequences in the messenger RNAs... (More)
The complex genetics of cancer, which allows tumours to grow and spread while bypassing the control circuitry of the cell, involves dysregulation of the genome, transcriptome and proteome. The importance of protein-coding genes such as growth factors and hormone receptors is well established. Recently, non-coding RNAs have emerged as important players in tumour development with potential to be explored as biomarkers and therapeutic targets. The aim of this thesis was to study the impact of small non-coding RNAs in cancer. MicroRNAs (miRNAs) are one of several types of ~20-30 nucleotide regulatory small non-coding RNAs. They regulate gene expression post-transcriptionally by base pairing to complementary sequences in the messenger RNAs (mRNAs) of protein-coding genes. We used traditional cloning and next-generation sequencing to map the small RNA transcriptome of breast cancer. By sequencing paired samples of tumour and normal breast tissue we detected differentially expressed miRNAs and found several hundred candidate new miRNA genes. We also identified a new type of small RNA derived from the RNA component of the vault particle, a ribonucleoprotein complex implicated in multi-drug resistance in tumour cells. These small vault RNAs (svRNAs) regulate gene expression similar to miRNAs. CYP3A4, an enzyme involved in drug metabolism, was validated as a target, establishing a possible link between the vault RNA and multi-drug resistance. Finally, we used microarrays to show that miRNA expression efficiently separates clinically relevant subgroups of bladder cancer. In summary, we have expanded the repertoire of small RNAs with findings that may have important clinical implications. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr Martens, John, Dept of Medical Oncology, Josefine Nefkens Insitute, Erasmus MC, Rotterdam, The Netherlands
organization
publishing date
type
Thesis
publication status
published
subject
keywords
microRNA, non-coding RNA, breast cancer, CYP3A4, bladder cancer
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2009:106
pages
130 pages
publisher
Department of Oncology, Clinical Sciences, Lund University
defense location
Segerfalk lecture hall, Wallenberg Neuroscience Center, BMC, Sölvegatan 17, Lund
defense date
2009-11-24 09:00
ISSN
1652-8220
ISBN
978-91-86253-94-3
language
English
LU publication?
yes
id
c91c9fac-8b46-450f-94c4-83e5ef166f23 (old id 1501164)
date added to LUP
2009-11-06 09:48:56
date last changed
2016-09-19 08:44:51
@phdthesis{c91c9fac-8b46-450f-94c4-83e5ef166f23,
  abstract     = {The complex genetics of cancer, which allows tumours to grow and spread while bypassing the control circuitry of the cell, involves dysregulation of the genome, transcriptome and proteome. The importance of protein-coding genes such as growth factors and hormone receptors is well established. Recently, non-coding RNAs have emerged as important players in tumour development with potential to be explored as biomarkers and therapeutic targets. The aim of this thesis was to study the impact of small non-coding RNAs in cancer. MicroRNAs (miRNAs) are one of several types of ~20-30 nucleotide regulatory small non-coding RNAs. They regulate gene expression post-transcriptionally by base pairing to complementary sequences in the messenger RNAs (mRNAs) of protein-coding genes. We used traditional cloning and next-generation sequencing to map the small RNA transcriptome of breast cancer. By sequencing paired samples of tumour and normal breast tissue we detected differentially expressed miRNAs and found several hundred candidate new miRNA genes. We also identified a new type of small RNA derived from the RNA component of the vault particle, a ribonucleoprotein complex implicated in multi-drug resistance in tumour cells. These small vault RNAs (svRNAs) regulate gene expression similar to miRNAs. CYP3A4, an enzyme involved in drug metabolism, was validated as a target, establishing a possible link between the vault RNA and multi-drug resistance. Finally, we used microarrays to show that miRNA expression efficiently separates clinically relevant subgroups of bladder cancer. In summary, we have expanded the repertoire of small RNAs with findings that may have important clinical implications.},
  author       = {Persson, Helena},
  isbn         = {978-91-86253-94-3},
  issn         = {1652-8220},
  keyword      = {microRNA,non-coding RNA,breast cancer,CYP3A4,bladder cancer},
  language     = {eng},
  pages        = {130},
  publisher    = {Department of Oncology, Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Small non-coding RNAs in cancer},
  volume       = {2009:106},
  year         = {2009},
}