bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1462: Exosome-derived miR-429 contributes to prostate cancer chemoresistance
Authors: Liu Yang , Xie Liye , Li Jing , Mizokami Atsushi , Keller Evan T. , Lu Yi , Zhang Jian 
Published: July 2017

Abstract
Prostate cancer (PCa) is the most common cancer in men and the 2nd leading cause of cancer-related death in the United States. Certain miRNAs, act as tumor promoting or inhibiting factors in tumor development, function primarily by targeting specific mRNAs for degradation or inhibition of translation of their targeted proteins. Emerging evidence indicates that exosomes play a key role in tumor-host crosstalk, and exosome secretion, composition, and functional capacity are altered as tumors progress to aggressive phenotypes. From our prior report, we have constructed a potential network of 29 deregulated miRNAs, including 19 up and 10 down, in exosome samples derived from two kinds of paclitaxel resistant PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). In this study, to further determine the roles of certain miRNAs derived from exosomes in chemoresistant cells, we firstly confirmed the lower expression level of miR-429 miRNA in the exosomes derived from the paclitaxel resistant PCa cells compared to their parental cells. In addition, when the miR-429 was over-expressed in PC3-TXR and DU145-TXR cells by stable transfection, epithelial-to-mesenchymal transition (EMT) markers significantly altered together with morphological changes. Overexpression of miR-429 decreased the tumor cell migration and invasion that associated with inactivation of PI-3K/AKT and Notch signaling pathways since the pathway specific inhibitors significantly diminished the transfected tumor cell migration and invasion. Finally, we found that overexpression of miRNA-429 significantly enhanced chemo-sensitivity of the chemoresistant PCa cells. These data suggested that exosome-derived miR-429 contributes to PCa chemoresistance and miR-429 may become a potential therapeutic target for PCa patients. This work was supported by Natural Science Foundation of China (NSFC) Key Project (81130046); NSFC (81171993; 81272415); Guangxi Projects of China (2013GXNSFEA053004; 2012GXNSFCB053004; 2013GXNSFBA019177; 1355004-5; 201201ZD004; GZPT13-35; 14122008-22; 11-031-05-K2; KY2015YB057; 14-045-12-K2).
Note: This abstract was not presented at the meeting.
Citation Format: Yang Liu, Liye Xie, Jing Li, Atsushi Mizokami, Evan T. Keller, Yi Lu, Jian Zhang. Exosome-derived miR-429 contributes to prostate cancer chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1462. doi:10.1158/1538-7445.AM2017-1462
Abstract 1466: QKI, a miRNA-200 target gene, suppresses epithelial-to-mesenchymal transition in oral squamous cell carcinoma cells
Authors: Ko Yoon Ho , Kim Eun Ju , Sun Der Sheng , Won Hye Sung , Ahn Young-Ho 
Published: July 2017

Abstract
Objectives:
The microRNA (miR)-200 family plays a major role in specifying the epithelial phenotype by preventing expression of the transcription repressors, ZEB1 and ZEB2, which are well-known regulators of epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether the miR-200 family members control RNA-binding protein quaking (QKI) which is a newly identified tumor suppressor and is regulated during EMT.
Methods:
We predicted that miR-200a and miR-200b could recognize QKI 3’-UTR by analyzing TargetScan and TCGA head and neck SCC dataset. To further verify the role of miR-200 on QKI in HNSCC, we carried out the functional study in CAL27 and HSC3 cells.
Results:
Forced expression of miR-200b/a/429 inhibited the expression of ZEB1 and ZEB2, and decreased cell migration in CAL27 and HSC3 cells. QKI expression was also suppressed by miR-200 over-expression, and the 3’-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and pro-tumor effects in vitro and in vivo studies of OSCC.
Conclusion:
QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis, contradictorily. We suggest that QKI and miR-200 could form a balancing feedback loop maintaining homeostatic responses to EMT-inducing signals.
Citation Format: Yoon Ho Ko, Eun Ju Kim, Der Sheng Sun, Hye Sung Won, Young-Ho Ahn. QKI, a miRNA-200 target gene, suppresses epithelial-to-mesenchymal transition in oral squamous cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1466. doi:10.1158/1538-7445.AM2017-1466
Abstract 1481: Determination of microRNA profile in lung cancer cell line treated with chemotherapy cisplatin (C), pemetrexed (P) or PC with bevacizumab (B) and its implication in resistance
Authors: Huang Chao H. , Motes Hannah C. , Sharma Siddarth , Kevern Jared , Borrego-Diaz Emma , Sharma Mukut 
Published: July 2017

Abstract
Background: Cellular microRNAs (miRNAs) regulate gene expression through modulation of messenger RNA transcription and are involved in epigenetic regulation, metastasis and cancer immunity. They have prognostic and therapeutic significance. The miRNAs associated with resistance in lung cancer without EGFR mutation are not yet known. We sought to determine the profile of miRNA of lung cancer cell lines without EGFR mutation treated with chemotherapy.
Methods: lung cancer cell lines HTB177 were treated with PC or PCB (0.05mg/mL Cisplatin, 0.05 mg/mL pemetrexed, 6.25 mg/mL Bevacizumab) for 24, 48, 72 and 144 hours. We obtained baseline miRNA prior to therapy and after treatment to determine the changes in miRNA profile using RT PCR technique. After 144 hours, we obtained miRNA profile of the cells that survived treatment to assess change in the miRNA profile. We chose miRNA that has been reported to influence on the outcome of lung cancer: Let 7 modulates RAS, miRNA 27 is involved as tumor suppressor gene, mir212 negatively regulates antiapoptotic protein PED, miR 375 down regulates ASH1 a transcription factor. Mir21 targets anti-apoptotic genes including PDCD4 and PTEN.
Results: We observed down regulation of these miRNA after 24h of treatment with PC and these miRNA then became upregulated after 48 hours, especially let 7f. In contrast, the treatment of PC with B caused upregulation of these miRNA, especially miR 27b and let 7f at 24 h and then decreased levels of upregulation at 48hours. These miRNA were not upregulated at 72h for both groups. The expression of miRNA 21 is upregulated 50 times in cells that survived treatment with PC or PCB at 144h.
Conclusions: The treatment using PC and PC with B in lung cancer cell lines regulates change in the profile of miRNA at different time points. There is a difference of the miRNA profile in these 2 treatment groups. miRNA 21 is upregulated in cells resistant to therapy. miRNA could be involved in the activity of chemotherapy and development of resistance.
Citation Format: Chao H. Huang, Hannah C. Motes, Siddarth Sharma, Jared Kevern, Emma Borrego-Diaz, Mukut Sharma. Determination of microRNA profile in lung cancer cell line treated with chemotherapy cisplatin (C), pemetrexed (P) or PC with bevacizumab (B) and its implication in resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2017-1481
Abstract 1498: Melatonin inhibits mitochondrial transcription factor A expression in glioblastoma U87MG cell culture inducing an anti-tumorigenic effect
Authors: Franco Daiane G. , Moretti Isabele F. , Marie Suely K. 
Published: July 2017

Abstract
Melatonin, the major hormone of pineal gland, has been described to induce intrinsic apoptosis in tumor cell, while it is inhibited in non-tumor cell. In tumor cell, melatonin stimulates intracellular production of reactive oxygen species (ROS) by a mechanism not completely understood. Here we propose that melatonin inhibits the expression of the mitochondrial transcription factor A (TFAM) in culture of glioblastoma (GBM) cell lineage, leading to an increase of the production of ROS. TFAM is an important mitochondrial protein that maintains the mitochondrial DNA (mtDNA) integrity and consequently the oxidative phosphorylation. Human U87MG GBM cell lineage was treated with melatonin (1 mM) for 72 h to evaluate the expression of TFAM and the mtDNA copy number through Real Time PCR. Proliferation, apoptosis, cell cycle and ROS production were also evaluated by cytometry (Muse - Millipore Corporation) and the results were normalized to control (vehicle: ethanol 0.3 %). Melatonin reduced the expression of TFAM in 17.5 % compared to the control group, but had no effect on the mtDNA copy number. Moreover, the incubation of U87MG with melatonin induced a reduction in cell proliferation in 14.24 % ± 4.3 compared to control, with an arrest of cell cycle in G0/G1 phase, which increased from 67.4 ± 3.71 % to 72.78 ± 3.18 % in the group treated with melatonin compared to the control. Production of ROS presented an increase of 7.1 %, with no significant effect on apoptosis. These results suggest that TFAM maybe a target for the melatonin function for an anti-tumorigenic effect through an increase of ROS production, inducing a delay in the cell cycle and a reduction of cell proliferation. The melatonin effect onTFAM maybe a novel signaling pathway that could be explored for the control of GBM progression.
Citation Format: Daiane G. Franco, Isabele F. Moretti, Suely K. Marie. Melatonin inhibits mitochondrial transcription factor A expression in glioblastoma U87MG cell culture inducing an anti-tumorigenic effect [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2017-1498
Abstract 15: Suppression of adaptive responses to targeted therapies by transcriptional inhibition
Authors: Rusan Maria , Li Kapsok , Li Yvonne , Christensen Camilla L. , Abraham Brian J. , Kwiatkowski Nicholas , Buczkowski Kevin , Bockorny Bruno , Chen Ting , Li Shuai , Zhang Haikuo , Terai Hideko , Tavares Tiffany , Zhang Tinghu , Kim Tae Jung , Silkes Michael , Mudianto Tenny , Tan Li , Shimamura Takeshi , Meyerson Matthew , Watanabe Hideo , Gray Nathanael S. , Young Richard A. , Wong Kwok-Kin , Hammerman Peter S. 
Published: July 2017

Abstract
Tumor cells become dependent on the expression of key genes that drive hallmark tumor traits, but these “addictions” also represent potential vulnerabilities for therapeutic intervention. Treating tumor cells with a small molecule inhibitor of the transcriptional kinase CDK7 selectively suppresses expression of key dependency genes in multiple cancers. Our previous work showed responses to the CDK7 inhibitor THZ1 were especially noteworthy in T cell leukemias, small cell lung cancers, and triple-negative breast cancers—tumor types where the prognoses are especially unfavorable. The genes whose expression is most sensitive to CDK7 inhibition and whose expression is essential for tumor cell survival are often associated with super-enhancers—clusters of constituent enhancers that are bound by unusually large amounts of transcription apparatus including CDK7 itself. This “Achilles’ cluster” of super-enhancer-associated genes thus represents the set of addictions of tumor cells whose expression is important for tumor cell survival. Transcriptional inhibition synergizes with targeted therapies in models of multiple tumor types. Treating tumors with therapies that target kinase proteins such as EGFR, FGFR, and KRAS leads to resistance, which is concurrent with changes in the activities of enhancers and super-enhancers and gene expression programs of resistant cells. Treating cells with a transcriptional inhibitor in addition to targeted therapies prevents “rewiring” of the gene expression program and increases cell death in tumor models. Thus transcriptional inhibition represents a promising avenue in both monotherapy and combination settings where drug resistance is acquired.
Citation Format: Maria Rusan, Kapsok Li, Yvonne Li, Camilla L. Christensen, Brian J. Abraham, Nicholas Kwiatkowski, Kevin Buczkowski, Bruno Bockorny, Ting Chen, Shuai Li, Haikuo Zhang, Hideko Terai, Tiffany Tavares, Tinghu Zhang, Tae Jung Kim, Michael Silkes, Tenny Mudianto, Li Tan, Takeshi Shimamura, Matthew Meyerson, Hideo Watanabe, Nathanael S. Gray, Richard A. Young, Kwok-Kin Wong, Peter S. Hammerman. Suppression of adaptive responses to targeted therapies by transcriptional inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 15. doi:10.1158/1538-7445.AM2017-15
Abstract 1501: Sideroflexin4: A novel regulator of iron metabolism in ovarian cancer
Authors: Paul Bibbin , Lynch Miranda , Torti Frank , Torti Suzy 
Published: July 2017

Abstract
The five year survival rate for women with ovarian cancer is 9-34%. This high mortality is due to late stage diagnosis, marginally effective treatment and frequent disease recurrence. Alterations in metabolism have been widely recognized as an important hallmark of cancer. Metabolism of the micronutrient iron is significantly altered in many cancers, including ovarian cancers. The expression of genes governing iron transport (TFR1 and FPN), iron storage (FTL and FTH) and iron regulation (IRP1 and IRP2) are significantly altered in ovarian cancer compared to normal ovarian epithelial cells, resulting in higher intratumoral iron retention. However, specific pathways of intracellular iron utilization that are altered in cancer cells, and the functional consequences of disrupting these pathways, remain poorly understood.
To identify pathways of iron utilization that are perturbed in ovarian cancer, we analyzed the expression of genes involved in iron metabolism using a publicly available microarray database of ovarian cancer and normal oviduct (GSE69428). We observed that sideroflexin4 (SFXN4), an inner mitochondrial membrane protein that is essential for mitochondrial respiratory homeostasis, was significantly upregulated (p= 0.002) in ovarian cancer patient samples. We screened several ovarian cancer cell lines and observed that SFXN4 was similarly up-regulated both at the mRNA and protein level when compared to normal human ovarian surface epithelial cells.
To test the role of SFXN4 in ovarian cancer cells we performed knockdown and overexpression studies. Knockdown of SFXN4 induced S and G2-phase cell cycle arrest and reduced the ability of MDAH2774 and SKOV3 ovarian cancer cells to form colonies. Further investigation revealed that modulation of SFXN4 alters mitochondrial respiration by affecting iron-sulfur cluster biogenesis. Thus, knock-out cells exhibited impaired respiratory activity and a phenotype similar to cells with defects in iron-sulfur cluster biogenesis, including increased IRP-IRE binding and a decrease in IRP1/ACO1 aconitase activity. Furthermore, SFXN4 knock-out decreased the activity of iron-sulfur cluster-containing enzymes such as mitochondrial aconitase and succinate dehydrogenase.
Based on these observations, we postulate that SFXN4 acts as a molecular mediator that channels the excess iron present in ovarian cancer cells to iron-sulfur cluster-dependent metabolic pathways that favor growth and metastasis. SFXN4 may be a potential druggable target in ovarian cancer.
Citation Format: Bibbin Paul, Miranda Lynch, Frank Torti, Suzy Torti. Sideroflexin4: A novel regulator of iron metabolism in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2017-1501
Abstract 1507: Fatty acid oxidation mediated autophagy regulation in triple negative breast cancer
Authors: Jung Kwang Hwa , Park Jun Hyoung , Sirupangi Tirupataiah , Vithayathil Sajna , Wong Lee-Jun , Kaipparettu Benny A. 
Published: July 2017

Abstract
Compared to hormone regulated/responsive (ER+) breast cancer (BC), triple negative BC (TNBC) patients have a worse overall survival, a significantly shorter disease-free survival, and a shorter post-recurrence survival. Using transmitochondrial cybrid (cybrid) (compares different mitochondria under a common defined nuclear background)-based discovery and validation in cell lines, patient derived xenografts (PDXs) and BC clinical tissues/data, we recently published that fatty acid oxidation (FAO) is a major energy pathway in TNBC. We also showed that FAO is a major regulator of Src activation by autophosphorylation at Src Y419 in metastatic TNBC. Our data suggest that inhibition of FAO induce cell growth inhibition. Short-term treatment of FAO inhibitors induces both cell cycle arrest and apoptosis. We observed cell cycle arrest in G1-S phase in FAO inhibitor treated TNBC cells. Apoptotic markers like cleaved Caspase-3 and cleaved PARP induced in FAO inhibited cells. Short-term treatment of FAO inhibitor also showed induction of AKT pathway. Further analysis on the role of FAO in TNBC suggests that FAO is a critical player in autophagy signaling in TNBC. Long-term treatment with FAO inhibitors or knockdown of FAO rate-limiting proteins carnitine palmitoyltransferase I (CPT1) induce autophagic cell death with beclin-1 and LC3-II induction in TNBC. However, no such phenomenon observed in estrogen receptor positive (ER+) breast cancer cell lines. Treatment with autophagy inhibitor 3-methyladenine (3-MA) abolished the FAO-induced cell growth inhibition and reduced beclin-1 and LC3-II induction. Ongoing studies using knock-down and over expression approaches focus on the role of specific pathways that are responsible for mitochondrial energy reprogramming regulated autophagy signaling in metastatic TNBC.
Citation Format: Kwang Hwa Jung, Jun Hyoung Park, Tirupataiah Sirupangi, Sajna Vithayathil, Lee-Jun Wong, Benny A. Kaipparettu. Fatty acid oxidation mediated autophagy regulation in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1507. doi:10.1158/1538-7445.AM2017-1507
Abstract 1522: Targeted gene therapy · c-MYC and hTERT in the scope
Authors: Rezzoug Francine , Thomas Shelia D. , Tella Segen , Miller Donald M. 
Published: July 2017

Abstract
In the past decade immunotherapy and kinase inhibitors have revolutionized the approach for cancer therapy, particularly for melanoma which has benefit from this new therapy in the last 5 years. Although, new treatment increase patient survival, there is no cure and treatments are often limited to a subtype of patients. Therefore there is still an urgent need for efficient therapy for melanoma. Among potential targets for cancer therapy, c-MYC and hTERT which are overexpressed in up-to 85% of all cancers are the most promising. The overexpression of hTERT provides indefinite division to cancer cells. Deregulation of c-MYC affect a large array of genes involved in cell cycle, proliferation/differentiation and apoptosis. Notably, both c-MYC and hTERT genes have in their promoter area a G-rich sequence that form secondary structure called G-quadruplex. These G-quadruplex structures are part of the silencers and are required for the repression of c-MYC or hTERT transcription. Mutations in the G-rich sequences of hTERT promoter destabilize the G-quadruplex and are associated with incidence of melanoma. We have shown that oligonucleotides encoding for the G-quadruples sequences of these genes promoter downregulate their respective gene expression and inhibit cell growth in different cell lines. We investigated the effect of targeting c-MYC or hTERT gene expression in melanoma cell lines using oligonucleotides targeted to the silencer G-quadruplex sequence. Four cell lines where investigated (SK-Mel-2, SK-Mel-3, SK-Mel-28 and A375) for the effect of Pu27 (targeting c-MYC) and Tert-FL (targeting hTERT) on cell proliferation using MTT assay. The treatment for 6 days resulted in 60% growth inhibition in the presence of Pu27 and 50% in the presence of Tert-FL for SK-Mel-2, SK-Mel-3, SK-Mel-28 while A375 was less sensitive. Gene expression evaluated by QRT-PCR showed down-regulation of c-MYC and hTERT in cell exposed to Pu27 and hTERT in cells exposed to Tert-FL. hTERT expression is regulated by c-MYC and in our experiment the down-regulation of c-MYC correlate with down-regulation of hTERT suggesting a cascade effect. In addition, SOX2 gene expression was also down-regulated by Pu27 suggesting an effect on the cancer stem cells (CSC). Our data demonstrate that oligonucleotides targeted to c-MYC and hTERT down-regulate gene expression associated with melanoma cell growth inhibition and possibly on metastasis.
Citation Format: Francine Rezzoug, Shelia D. Thomas, Segen Tella, Donald M. Miller. Targeted gene therapy · c-MYC and hTERT in the scope [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1522. doi:10.1158/1538-7445.AM2017-1522