Estrogen-induced upregulation and 3 '-UTR shortening of CDC6

3'-Untranslated region (UTR) shortening of mRNAs via alternative polyadenylation (APA) has important ramifications for gene expression. By using proximal APA sites and switching to shorter 3'-UTRs, proliferating cells avoid miRNA-mediated repression. Such APA and 3'-UTR shortening events may explain the basis of some of the proto-oncogene activation cases observed in cancer cells. In this study, we investigated whether 17 beta-estradiol (E2), a potent proliferation signal, induces APA and 3'-UTR shortening to activate proto-oncogenes in estrogen receptor positive (ER+) breast cancers. Our initial probe based screen of independent expression arrays suggested upregulation and 3'-UTR shortening of an essential regulator of DNA replication, CDC6 (cell division cycle 6), upon E2 treatment. We further confirmed the E2- and ER-dependent upregulation and 3'UTR shortening of CDC6, which lead to increased CDC6 protein levels and higher BrdU incorporation. Consequently, miRNA binding predictions and dual luciferase assays suggested that 3'-UTR shortening of CDC6 was a mechanism to avoid 3'-UTR-dependent negative regulations. Hence, we demonstrated CDC6 APA induction by the proliferative effect of E2 in ER+ cells and provided new insights into the complex regulation of APA. E2-induced APA is likely to be an important but previously overlooked mechanism of E2-responsive gene expression.


Estrogen-induced upregulation and 3’-UTR shortening of CDC6
Akman, H. Begüm; Erson Bensan, Ayşe Elif; Department of Biology (2013)
Alternative polyadenylation (APA) may cause mRNA 3’-UTR (untranslated region) shortening in different physiological conditions and/or disease states. About half of mammalian genes use alternative cleavage and polyadenylation to generate multiple mRNA isoforms differing in their 3′-UTRs. Consequently, 3’-UTR shortening of mRNAs via APA has important consequences for gene expression. Studies showed that, by preferential use of proximal APA sites and switching to shorter 3’-UTRs, proliferating cells can avoid ...
3 ' UTR shortening and EGF signaling: implications for breast cancer
AKMAN, Hesna Begum; ÖYKEN, MERVE; TUNCER, Taner; Can, Tolga; Erson Bensan, Ayşe Elif (2015-12-15)
Alternative polyadenylation (APA) plays a role in gene expression regulation generally by shortening of 3'UTRs (untranslated regions) upon proliferative signals and relieving microRNA-mediated repression. Owing to high proliferative indices of triple negative breast cancers (TNBCs), we hypothesized APA to cause 3'UTR length changes in this aggressive subgroup of breast cancers. Our probe-based meta-analysis approach identified 3'UTR length alterations where the significant majority was shortening events (si...
Use of an intronic polyadenylation site in breast cancer
Köksal Bıçakcı, Gözd; Erson Bensan, Ayşe Elif; Department of Molecular Biology and Genetics (2020)
Alternative polyadenylation is an important mRNA processing step in which the length and/or the sequence of 3’UTR of mRNAs are altered. This change in 3’UTRs may have significant effects on mRNA stability, localization and translational efficiency. One of the APA types, called intronic polyadenylation (IPA), occurs on intronic sites rather than 3’UTRs. Recent evidence shows that almost 20% of human genes have a poly(A) site in at least one intron. In fact, some introns even may have more than one poly(A) si...
Phenotypical characterization of microRNA-106B overexpression in MCF10A breast cell line
Saygılı, Cansaran; Erson Bensan, Ayşe Elif; Department of Biology (2013)
MicroRNAs are small non-coding RNAs which regulate gene expression by binding to 3’UTR of their target mRNAs. Deregulated expression of microRNAs is detected in many pathologies including different types of cancers. miR-106b, is a member of miR-106b-25 cluster and overexpressed in many cancers including breast cancer. Based on miR-106b overexpression, we hypothesized that miR-106b may be an oncogene candidate. To explore miR-106b related phenotypes, we used an already miR-106b transfected model cell line sy...
Immunoadjuvant action of plasmid DNA in liposomes
Gürsel, Mayda; Ozkan, M; Özcengiz, Gülay (1999-03-17)
Bacterial DNA and oligodeoxynucleotides containing immunostimulatory sequences with a CpG motif stimulated a Th1 type response in vivo. The adjuvant action of a non-coding plasmid DNA derived from pRc/CMV HBS (encoding the S region of hepatitis B surface antigen, HBsAg) in mice was investigated. The role of methylation on the adjuvanticity of the plasmid as well as the effect of vaccine formulation employed on the outcome of antigen-specific humoral and cellular responses were also studied. The results demo...
Citation Formats
B. H. AKMAN, T. Can, and A. E. Erson Bensan, “Estrogen-induced upregulation and 3 ’-UTR shortening of CDC6,” NUCLEIC ACIDS RESEARCH, pp. 10679–10688, 2012, Accessed: 00, 2020. [Online]. Available: