497 research outputs found
Targeting long non-coding RNAs (lncRNAs) with oligonucleotides in cancer therapy
This document is the Accepted Manuscript version of a published work that appeared in final form in Translational Cancer Research. To access the final edited and published work see http://dx.doi.org/10.21037/tcr.2016.10.63No abstrac
The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells.
Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and -insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies.Breast Cancer No
RBM5/LUCA-15 — Tumour Suppression by Control of Apoptosis and the Cell Cycle?
The candidate tumour suppressor gene, LUCA-15, maps to the lung cancer tumour suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four alternatively spliced transcripts, which have been shown to function as regulators of apoptosis, a fact that may have a major significance in tumour regulation. This review highlights evidence that implicates the LUCA-15 locus in the control of apoptosis and cell proliferation, and reports observations that significantly strengthen the case for tumour suppressor activity by this gene
Looking Back at International Synchrotron Radiation Instrumentation
With the 11th International Synchrotron Radiation Instrumentation coming up in July 2012 in Lyons, France, we thought it might be of interest to our readers to review all the past meetings in this series. We thank Denny Mills of the APS, Argonne for putting the list together. Prior to these larger meetings, and in the early days, facilities held their own meetings similar to the user meetings of today. However, the meeting held at ACO in Orsay, France in 1977 was the first such meeting with an international flavor and so it is on the list. However it is not counted as number 1 since it was agreed way back to start the numbering with the 1982 DESY meeting. The 2005 USA National Meeting scheduled at CAMD in Baton Rouge had to be canceled due to Hurricane Katrina. It was ultimately held in 2007, with the CLS hosted meeting the following year. And a personal note from the magazine - Synchrotron Radiation News was born at the 1987 meeting in Madison, Wisconsin with a proposal that was put to a special session of the meeting organized by Susan Lord. Initial proposals were to model it after the CERN Courier, but it soon adopted its own distinct flavor
GAS5 lncRNA Modulates the Action of mTOR Inhibitors in Prostate Cancer Cells
Background There is a need to develop new therapies for castrate-resistant prostate cancer (CRPC) and growth arrest-specific 5 (GAS5) long non-coding RNA (lncRNA), which riborepresses androgen receptor action, may offer novel opportunities in this regard. GAS5 lncRNA expression declines as prostate cancer cells acquire castrate-resistance, and decreased GAS5 expression attenuates the responses of prostate cancer cells to apoptotic stimuli. Enhancing GAS5 lncRNA expression may therefore offer a strategy to improve the effectiveness of chemotherapeutic agents. GAS5 is a member of the 5' terminal oligopyrimidine gene family, and we have therefore examined if mTOR inhibition can enhance cellular GAS5 levels in prostate cancer cells. In addition, we have determined if GAS5 lncRNA itself is required for mTOR inhibitor action in prostate cancer cells, as recently demonstrated in lymphoid cells. Method The effects of mTOR inhibitors on GAS5 lncRNA expression and cell proliferation were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNA and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action. Results Treatment with rapamycin and rapalogues increased cellular GAS5 levels and inhibited culture growth in both androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU145) cells. GAS5 silencing in both LNCaP and 22Rv1 cells decreased their sensitivity to growth inhibition by mTOR inhibitors. Moreover, transfection of GAS5 lncRNA sensitized PC-3 and DU145 cells to mTOR inhibitors, resulting in inhibition of culture growth. Conclusion mTOR inhibition enhances GAS5 transcript levels in some, but not all, prostate cancer cell lines. This may in part be related to endogenous levels of GAS5 expression, which tend to be lower in prostate cancer cells representative of advanced disease, particularly since current findings demonstrate a role for GAS5 lncRNA in mTOR inhibitor action in prostate cancer cells
Correlation Between Phase Competition and the Nucleation of a Griffiths Phase in (La1-yPry)0.7Ca0.3Mn16/18O3
Detailed analyses of the temperature-dependent zero field ac susceptibility
of prototypical phase-separated (La1-yPry)0.7Ca0.3Mn16/18O3, 0 < y < 1, reveal
features consistent with the presence of a Griffiths phase (GP), viz., an
inverse susceptibility characterized by power law with 0.05 < lamda < 0.33 as y
decreases towards yc < 0.85. Beyond yc = 0.85, the GP is suppressed. These
data, combined with previous neutron diffraction measurements, enable a phase
diagram summarizing the evolution of the GP with composition to be constructed
for this system; in particular, it shows that the disorder relevant for the
establishment of such a phase is linked closely to the relative volume
fractions of the phase separated antiferromagnetic and ferromagnetic
components, even when the recently estimated double exchange (DE) linked
percolation threshold is exceeded. The influence of electron-phonon coupling
can also be seen through oxygen isotope effects.Comment: 4 page
Nucleus pulposus cells as competent phagocytes to clear apoptotic cells: mission applicable or impossible? Authors' response
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