Small non-coding RNAs in cancer

Research output: ThesisDoctoral Thesis (compilation)

Standard

Small non-coding RNAs in cancer. / Persson, Helena.

Department of Oncology, Clinical Sciences, Lund University, 2009. 130 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

Persson, H 2009, 'Small non-coding RNAs in cancer', Doctor, Oncology and Pathology, MV.

APA

Persson, H. (2009). Small non-coding RNAs in cancer. Department of Oncology, Clinical Sciences, Lund University.

CBE

Persson H. 2009. Small non-coding RNAs in cancer. Department of Oncology, Clinical Sciences, Lund University. 130 p.

MLA

Persson, Helena Small non-coding RNAs in cancer Department of Oncology, Clinical Sciences, Lund University. 2009.

Vancouver

Persson H. Small non-coding RNAs in cancer. Department of Oncology, Clinical Sciences, Lund University, 2009. 130 p. (Lund University Faculty of Medicine Doctoral Dissertation Series ).

Author

Persson, Helena. / Small non-coding RNAs in cancer. Department of Oncology, Clinical Sciences, Lund University, 2009. 130 p.

RIS

TY - THES

T1 - Small non-coding RNAs in cancer

AU - Persson, Helena

N1 - Defence details Date: 2009-11-24 Time: 09:00 Place: Segerfalk lecture hall, Wallenberg Neuroscience Center, BMC, Sölvegatan 17, Lund External reviewer(s) Name: Martens, John Title: Dr Affiliation: Dept of Medical Oncology, Josefine Nefkens Insitute, Erasmus MC, Rotterdam, The Netherlands ---

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - microRNA

KW - non-coding RNA

KW - breast cancer

KW - CYP3A4

KW - bladder cancer

M3 - Doctoral Thesis (compilation)

SN - 978-91-86253-94-3

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Oncology, Clinical Sciences, Lund University

ER -