scholarly journals SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer

Sci ◽  
2020 ◽  
Vol 2 (2) ◽  
pp. 24
Author(s):  
Carole Ferraro-Peyret ◽  
Marjan E. Askarian-Amiri ◽  
Debina Sarkar ◽  
Wayne R. Joseph ◽  
Herah Hansji ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Glucose Deprivation ◽  
Breast Cancer Cell Lines ◽  
Oestrogen Deprivation

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

scholarly journals SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer

Sci ◽  
2021 ◽  
Vol 3 (2) ◽  
pp. 26
Author(s):  
Carole Ferraro-Peyret ◽  
Marjan E. Askarian-Amiri ◽  
Debina Sarkar ◽  
Wayne R. Joseph ◽  
Herah Hansji ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Glucose Deprivation ◽  
Breast Cancer Cell Lines ◽  
Oestrogen Deprivation

Endoplasmic reticulum (ENR) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are upregulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation upregulates SOX2OT expression. This upregulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ENR stress reprogramming of breast cancer cells.

scholarly journals Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15

2019 ◽  
Vol 145 (9) ◽  
pp. 2478-2487 ◽  
Author(s):  
Liang‐Chih Liu ◽  
Yuan‐Liang Wang ◽  
Pei‐Le Lin ◽  
Xiang Zhang ◽  
Wei‐Chung Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Cells

scholarly journals High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells

2017 ◽  
Vol 95 (2) ◽  
pp. 289-294 ◽  
Author(s):  
Ali Burak Ozkaya ◽  
Handan Ak ◽  
Hikmet Hakan Aydin
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Survival Function ◽  
Active Form ◽  
Breast Cancer Cell Lines ◽  
Transcriptomic Profile

Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.

scholarly journals Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Baiyao Wang ◽  
Jieling Zheng ◽  
Rong Li ◽  
Yunhong Tian ◽  
Jie Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Inverse Correlation ◽  
Deubiquitinating Enzyme ◽  
Downstream Target ◽  
Damage Response

Abstract Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.

scholarly journals ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells

2016 ◽  
Vol 11 (1) ◽  
Author(s):  
Herah Hansji ◽  
Euphemia Y. Leung ◽  
Bruce C. Baguley ◽  
Graeme J. Finlay ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Cells

scholarly journals Long Noncoding RNA CAMTA1 Promotes Proliferation and Mobility of the Human Breast Cancer Cell Line MDA-MB-231 via Targeting miR-20b

2018 ◽  
Vol 26 (4) ◽  
pp. 625-635 ◽  
Author(s):  
Pengwei Lu ◽  
Yuanting Gu ◽  
Lin Li ◽  
Fang Wang ◽  
Xue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cell Line ◽  
Long Noncoding Rna ◽  
Human Breast Cancer ◽  
Noncoding Rna ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast

Breast cancer is a serious threat to women’s physical and psychological health. Long noncoding RNA CAMTA1 (lncCAMTA1) was believed to be related with tumor progression, but its role in breast cancer is not clear. The human breast cancer cell line MDA-MB-231 was used to investigate the effect of lncCAMTA1 on cell viability, migration/invasion, and apoptosis. The expression of lncCAMTA1, miR-20b, and VEGF in MDA-MB-231 were measured after corresponding transfections. Binding effects between lncCAMTA1 and miR-20b, miR-20b, and VEGF 3′-UTR were measured. The effects of miR-20b and VEGF on breast cancer cells were also assessed after transfections. The phosphorylation levels of the MAPK/ERK and JAK/STAT3 pathways were determined to assess the effect of VEGF. The results showed that lncCAMTA1 expression promoted cell viability and migration/invasion, while knockdown of lncCAMTA1 promoted cell apoptosis via binding with miR-20b. lncCAMTA1 negatively regulated miR-20b expression. VEGF was a target of miR-20b, leading to the modification of the phosphorylation levels of MAPK, ERK, JAK, STAT1, and STAT3. Our findings suggested that lncCAMTA1 might promote proliferation and mobility of human breast cancer cells via binding with miR-20b. VEGF was a direct target of miR-20b and regulated activation of the MAPK/ERK and JAK/STAT3 signaling pathways. Therefore lncCAMTA1 has potential as a novel cancer diagnostic marker and as a putative novel therapeutic target for breast cancer treatment.

scholarly journals Pygenic Acid A (PA) Sensitizes Metastatic Breast Cancer Cells to Anoikis and Inhibits Metastasis In Vivo

2020 ◽  
Vol 21 (22) ◽  
pp. 8444
Author(s):  
Ga-Eun Lim ◽  
Jee Young Sung ◽  
Suyeun Yu ◽  
Younmi Kim ◽  
Jaegal Shim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Cell Lines ◽  
Syngeneic Mouse Model ◽  
Apoptosis Protein ◽  
4T1 Cells

Metastasis is the main cause of cancer-related deaths. Anoikis is a type of apoptosis caused by cell detachment, and cancer cells become anoikis resistant such that they survive during circulation and can successfully metastasize. Therefore, sensitization of cancer cells to anoikis could prevent metastasis. Here, by screening for anoikis sensitizer using natural compounds, we found that pygenic acid A (PA), a natural compound from Prunella vulgaris, not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis. Apoptosis protein array and immunoblotting analysis revealed that PA downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells. Interestingly, PA decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1. Ectopic expression of active STAT3 attenuated PA-induced anoikis sensitivity. Although PA activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation, which could be due to PA-induced defects in autophagy flux. PA also decreased metastatic characteristics, such as cell invasion, migration, wound closure, and 3D growth. Finally, lung metastasis of luciferase-labeled 4T1 cells decreased following PA treatment in a syngeneic mouse model when compared with the control. These data suggest that PA sensitizes metastatic breast cancer cells to anoikis via multiple pathways, such as inhibition of pro-survival pathways and activation of ER stress and autophagy, leading to the inhibition of metastasis. These findings suggest that sensitization to anoikis by PA could be used as a new therapeutic strategy to control the metastasis of breast cancer.

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