Deregulated APA and cancer specific APA isoforms

Date

2018-07-01

Author

Begik, Oguzhan
Ercan, Melda
Cingoz, Harun
Can, Tolga
ÖYKEN, MERVE
Erson Bensan, Ayşe Elif

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

170
views

0
downloads

Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. We developed a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we found a significant shift in usage of poly(A) signals in six common tumor types compared to normal tissues. We further defined specific subsets of APA events to efficiently classify cancer types/subtypes. Triple negative breast cancers, for example, have specific 3'UTR length alterations where the significant majority are shortening events (70%, 113 of 165) of mostly proliferation-related transcripts compared with normal breast tissue. Such shortening events correlate with increased protein levels and relapse free survival of patients, suggesting functional significance of isoform variability. In line with this isoform diversity, we also detected deregulated expression of mRNA polyadenylation complex proteins in breast cancer cells. Of note, APA proteins are responsive to proliferative signals including estrogen and epidermal growth factor, suggesting a potential explanation to 3'-end isoform diversity in cancer cells. Overall, our study offers a computational and experimental approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.

URI

https://hdl.handle.net/11511/41615

DOI

https://doi.org/10.1158/1538-7445.am2018-2360

Collections

Department of Computer Engineering, Conference / Seminar

Suggestions

OpenMETU
Core

Alternative Polyadenylation patterns for novel gene discovery and classification in cancer Beğik, Oğuzhan; Öyken, Merve; Can, Tolga; Erson Bensan, Ayşe Elif (2017-06-03) Certain aspects of diagnosis, prognosis and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1,045 cancer patients and found a significant shift in usage of poly(A) signals in cancers. Using machine-learning techniques, we further def...
Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer BEGIK, Oguzhan; ÖYKEN, MERVE; ALICAN, Tuna Cinkilli; Can, Tolga; Erson Bensan, Ayşe Elif (2017-07-01) Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A) signals in common tumor types (breast, colon, lung, prostate, gastric...
Novel ferrocenyl pyrazoles inhibit breast cancer cell viability via induction of apoptosis and inhibition of PI3K/Akt and ERK1/2 signaling Atmaca, Harika; Ozkan, Ayse Nur; Zora, Metin (2017-02-01) Despite the advances in early detection and targeted therapies, chemotherapy is still of vital importance in breast cancer treatment. However, development of drug resistance and serious side effects limits their usage. Thus, there is an urgent need for safer and more effective agents against breast cancer. We have previously described the synthesis of a number of pyrazole derivatives, and in the current study, we have investigated the effects of two different ferrocenyl pyrazole (FP) derivates, 5-ferrocenyl...
Capture of rare circulating tumor cells from blood on bio-activated oxide surface inside microfluidic channels Ateş, Hatice Ceren; Külah, Haluk; Özgür, Ebru; Department of Micro and Nanotechnology (2018) Isolation and characterization of circulating tumor cells (CTCs) have important clinical significance in terms of prognosis and early detection of response to treatment. Moreover, downstream characterization of CTCs may help better patient stratification and therapy guidance. However, CTCs are extremely rare (~10 CTCs/1010 peripheral blood cells) and highly sensitive, and specific technology is required for their isolation. Rapidly developing microfluidic technologies offer variety of advantages in rare cel...
Modeling and Characterization of Nanomedicine Transport within Tumor Microenvironment across Scales Akalın, Ali Aykut; Özçelikkale, Altuğ (2022-09-19) Despite significant advances in recent decades, diagnosis and treatment of cancer remain to be a major challenge. Advances in nanotechnology have enabled numerous nanoparticle (NP) formulations for efficient delivery of drugs and diagnostic agents to the target tumor site. The size, shape, charge, and surface characteristics of so-called nanomedicine can be tuned to affect the interactions of the NP with the physiological environment [1]. However, design efforts to develop nanomedicine for efficient deliver...

Citation Formats

O. Begik, M. Ercan, H. Cingoz, T. Can, M. ÖYKEN, and A. E. Erson Bensan, “Deregulated APA and cancer specific APA isoforms,” 2018, vol. 78, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41615.