bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1800: miR-376b and miR-4668 predict therapeutic response to sunitinib in metastatic renal cell carcinoma
Authors: Kovacova Julia , Juracek Jaroslav , Poprach Alexandr , Buchler Tomas , Fiala Ondrej , Radova Lenka , Svoboda Marek , Kopkova Alena , Vecera Marek , Slaby Ondrej 
Published: August 2019

Abstract
Introduction: Metastatic renal cell carcinoma (mRCC) is routinely treated with sunitinib, a tyrosine kinase inhibitor (TKI) of VEGF signalisation. Although disease eventually progresses in most mRCC patients, length of progression-free survival (PFS) is ranging from few weeks up to more than 24 months. Patients with initial resistance to sunitinib could be redirected to other therapeutical options, as there are several other TKIs available for use in second and third line. However, without a reliable biomarker no result can be predicted. MicroRNAs (miRNAs) belong to class of short non-coding RNAs and could serve as biomarkers of therapy response due to their unique character and presence in tissues and body fluids. Their biomarker potential has been discussed concerning many diseases including mRCC, but current knowledge is very weak, has several discrepancies and is acquired on relatively small cohorts.
Material and method: Candidate microRNAs have been chosen based on global expression profiling using Affymetrix GeneChip 4.0 in 47 samples of FFPE mRCC tissue of patients treated with sunitinib (good response n=25, PFS longer than 17 months; poor response n=22, PFS shorter than 9 months). Validation was performed using qRT-PCR TaqMan assays on an independent cohort of 136 FFPE samples from mRCC patients treated with sunitinib with variable length of PFS. Local ethical committees at all involved centres approved the study protocol. The study was performed according to the World Medical Association Declaration of Helsinki and all patients signed an informed consent.
Results and discussion: Of all tested miRNAs, expression of miR-4668-5p and miR-376b was the most significantly deregulated in non-responding patients with high statistical significance (p&gt;0,005) and combined AUC higher than 0,8. Although other independent validations are necessary, microRNAs presented here seem to be very promising as tools for therapy personalization.
Conclusion: We have successfully validated miR-4668-5p and miR-376b to have predictive potential in estimation of therapeutical response to sunitinib. Further functional analyses could shed more light on their involvement in development of therapy resistance. This work was supported by Ministry of Health of the Czech Republic, grant nr. NV18-03-00554. All rights reserved.
Citation Format: Julia Kovacova, Jaroslav Juracek, Alexandr Poprach, Tomas Buchler, Ondrej Fiala, Lenka Radova, Marek Svoboda, Alena Kopkova, Marek Vecera, Ondrej Slaby. miR-376b and miR-4668 predict therapeutic response to sunitinib in metastatic renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1800.
Abstract 1803: Openarray profiling of the systemic change of microRNAs in rhenium-188 liposome treated human head and neck cancer cells
Authors: Lin Bing-Ze , Chang Chun-Yuan , Chang Chih-Hsien , Lee Yi-Jang 
Published: August 2019

Abstract
Purpose188Re-liposome has been used for evaluating the theranostic efficacy in various human cancers. However, whether the therapeutic efficacy of 188Re-liposome directly related to microRNAs regulation and specific signaling pathways are largely unknown. In this project, we investigated the 188Re-liposome induced systemic microRNA expressive responses in human head and neck cancer (HNSCC) cells.
Methods
The FaDu-3R cells were implanted into the nude mice at the position of buccal cavity. After two weeks of implantation, the tumors were palpable and the bioluminescent imaging indicated the location of this orthotopic tumor model. The PEGylated 188Re-liposome was intravenously injected single and dual dose respectively. We harvested all of the tumors after 188Re-liposome injection one month ago, and used Taqman Openarray MicroRNA (Thermo, USA) to detect the expression of miRNAs in different groups. The dataset we observed was further analyzed by using Ingenuity Pathway Analysis (IPA) software to establish the molecular signaling pathway of 188Re-liposome radiopharmaceutical.
Results
Quantification of the photon signals showed that the tumor growth of the dual 188Re-liposome treated mice was slower than that of control ones. The survival rate of 188Re-liposome treated animals were also better than control ones. The microRNA Openarray showed that, compared to untreated control, 17 miRNA were significantly changed in expressive levels over 5 fold after 188Re-liposome treatment. Subsequently, we used IPA to determine the role of these miRNA, and found these miRNA with oncogenic and tumor suppressive properties were down-regulated and up-regulated, respectively. Among them, we focused on miR-152-5p that is closed related to cancer occurrence and development, and showed that knockdown of miR-152-5p could decreased the effects of 188Re-liposome on suppressing the growth of HNSCC xenograft tumors.
Conclusion
HNSCC tumor model treated with dual dose of 188Re-liposome exhibited significant response to this radiopharmaceutical. We also found that 17 miRNA could be gsignificantly re-regulated, and miR-152-5p is one example to be involved in mediating the efficacy of 188Re-liposome. Targeting on specific miRNA may enhance the application value of 188Re-liposome.in cancer treatment.
Citation Format: Bing-Ze Lin, Chun-Yuan Chang, Chih-Hsien Chang, Yi-Jang Lee. Openarray profiling of the systemic change of microRNAs in rhenium-188 liposome treated human head and neck cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1803.
Abstract 1813: Depletion of PCAT1 in head and neck cancer cells limits tumor growth by regulating c-Myc, AKT1 and MAPK signalling pathways
Authors: Sur Subhayan , Steele Robert , Ray Ratna B. 
Published: August 2019

Abstract
Head and neck squamous cell carcinoma (HNSCC) represents one of the most common malignancies worldwide with a high mortality rate mainly due to lack of early detection markers, frequent metastasis and aggressive phenotype. Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancers. Up-regulation of prostate cancer-associated transcript 1 (PCAT1) in TCGA dataset of HNSCC was noted. In this study, we aimed to evaluate role of the PCAT1 in HNSCC. During validation, we observed up-regulation of PCAT1 in HNSCC patient samples and cell lines. siRNA mediated knock-down of PCAT1 significantly reduced cell proliferation, sphere formation and wound healing in HNSCC cell lines (JHU29 and Cal27). Mechanistic study revealed a significant down-regulation of c-Myc and AKT1 in both RNA and protein levels upon knockdown of PCAT1 in HNSCC cell lines. In-silico analysis suggested a significant positive correlation between PCAT1 and c-Myc or PCAT1 and AKT1 in HNSCC cell lines. Subsequently, we observed modulation of MAPK signalling by activation of p38 and apoptosis signal-regulating kinase 1 (ASK1) upon knockdown of PCAT1, and induction of apoptosis as evident of caspase 9 activation and PARP cleavage. Introduction of PCAT1 into HNSCC xenograft tumors displayed a reduction in tumor volume. Together our data demonstrated an important role of the PCAT1 in HNSCC progression and has potential as a therapeutic candidate.
Citation Format: Subhayan Sur, Robert Steele, Ratna B. Ray. Depletion of PCAT1 in head and neck cancer cells limits tumor growth by regulating c-Myc, AKT1 and MAPK signalling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1813.
Abstract 1816: Tumor suppressor LINC02487 inhibits oral cancer cell migration and invasion through directly binding protein USP17
Authors: Feng Lu , Qiu Feng , Zhang Jianjun , Sun Minglei , Chen Wantao , Qiu Weiliu 
Published: August 2019

Abstract
Objective: The aim of this study is to explore the functions and mechanisms of long non-coding RNA LINC02487 in oral squamous cell carcinoma(OSCC).
Materials and methods: Relative expression level of LINC02487 in OSCC cell lines and samples were examined by qRT-PCR. Intracellular localization was done using RNA fluorescence in situ hybridization. LINC02487 was cloned into pCMV-puro vector, and transfected into OSCC cell lines HN6 and HN30 by lentivirus. Cell functions as proliferation, apoptosis, cell cycle, migration and invasion were examined subsequently. RNA binding protein was explored by ChIRP-MS. And protein expression was determined by western-blotting assay.
Results: Previous data showed a downregulation of LINC02487 in OSCCs. Here we confirmed the lower expression of LINC02487 in 6 OSCC cell lines comparing with immortalized normal oral epithelial cell lines, and in 50 OSCC samples comparing with paired adjacent normal tissue. LINC02487 was located in cytoplasm, aggregated around nuclei membrane. Overexpression of LINC02487 significantly suppressed cell migration and invasion, increased the ratio of cells in G1 phase, with a minor influence on cell proliferation and apoptosis. Furtherly, LINC02487 was found directly binding to USP17, a deubiquitinating enzyme, and regulating cell migration and invasion through USP17 expression.
Conclusion: Our study confirmed that long non-coding RNA LINC02487 was downregulated in paired OSCC samples and cell lines. It acts as a tumor suppressor through its directly binding protein USP17.
Citation Format: Lu Feng, Feng Qiu, Jianjun Zhang, Minglei Sun, Wantao Chen, Weiliu Qiu. Tumor suppressor LINC02487 inhibits oral cancer cell migration and invasion through directly binding protein USP17 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1816.
Abstract 1820: Circular RNAs contribute to neuroblastoma pathogenesis
Authors: Klironomos Filippos , Danssmann Clara , Naderi Julian , Winkler Annika , Luz Uschi , Hundsdoerfer Patrick , Eggert Angelika , Toedling Joern , Hertwig Falk , Schulte Johannes H. , Fuchs Steffen 
Published: August 2019

Abstract
Circular RNAs (circRNAs), a noncoding RNA class originating from alternative splicing, are highly abundant in neural tissues and can regulate gene expression by binding to and inhibiting microRNAs and RNA-binding proteins. We explored whether circRNAs influence pathogenesis in neuroblastoma, the most common solid extracranial tumor of childhood. We performed whole-transcriptome sequencing of primary neuroblastoma samples to identify candidate circRNAs, which were validated in a neuroblastoma cell line panel. Overexpression and knockdown models were created to investigate their impact on cell viability, proliferation, apoptosis and differentiation. We identified 4,482 unique circRNA backsplicing junctions involving 2,080 genes in 69 neuroblastoma samples from all risk groups. Candidate circRNA expression did not correlate with host gene expression, indicating independent regulatory mechanisms. Principal component analysis was conducted using tumor circRNA expression. MYCN-amplified tumors clustered tightly together, demonstrating that variations in circRNA expression identify MYCN-amplified neuroblastomas as do gene expression patterns. Comparing our RNA sequencing data with other cancers and healthy fetal brain tissue revealed a circRNA subset specifically upregulated in neuroblastoma that included a circRNA derived from the ARID1A tumor suppressor gene. Cell fractionization and RNA FISH localized circARID1A to the cytoplasm, where it could interact with miRNAs and RNA-binding proteins for functional consequences. Specific circARID1A knockdown reduced cell numbers and viability, and induced neurite outgrowth and differentiation markers. Neither knockdown, nor overexpression of circARID1A influenced ARID1A mRNA and protein levels. Ongoing efforts applying bioinformatics methods to investigate the mechanism of action have identified several binding sites of microRNAs and RNA-binding proteins enriched in the circARID1A sequence. We demonstrate that circRNAs are expressed in neuroblastomas unrelated to host gene expression, and that their expression can be used to cluster MYCN-amplified tumors. As one in a set of upregulated circRNAs, circARID1A acts in a tumor-promoting manner in neuroblastoma cell lines independent of the host gene.
Citation Format: Filippos Klironomos, Clara Danssmann, Julian Naderi, Annika Winkler, Uschi Luz, Patrick Hundsdoerfer, Angelika Eggert, Joern Toedling, Falk Hertwig, Johannes H. Schulte, Steffen Fuchs. Circular RNAs contribute to neuroblastoma pathogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1820.
Abstract 1822: A mitochondrial pfeRNA associates with Far Upstream Element Binding Protein 1 (FUBP1) to promote lung adenocarcinoma tumorigenesis
Authors: Fackche Nadege T. , Mei Yuping , Ito Tomoaki , Garner Matthew , Brock Malcolm 
Published: August 2019

Abstract
Background: Protein Functional Effector RNAs (pfeRNAs) are novel small non-coding RNA molecules with great prognostic and diagnostic potential for NSCLC. They feature direct binding to, and regulation of phosphorylated proteins involved in lung cancer tumorigenesis pathways. Using next-generation sncRNA deep sequencing, we have identified a mitochondrial pfeRNA (mtpfeRNA) that could play a key role in tumorigenesis and cancer development of lung adenocarcinoma (ADC).
Methods: Using next-generation sncRNA deep sequencing, we analysed ADC and human normal bronchial epithelial (HBE) cell lines; and biospecimens including matched biopsy-proven ADC tissue, histologically normal adjacent lung tissue, benign lymph node, and (iv) malignant lymph nodes; Identifying a mitochondrial pfeRNA that could play critical roles in lung cancer tumorigenesis. Next, we examined the impact of this mtpfeRNA on lung ADC cell line viability. Liquid chromatography-tandem mass spectrometry analysis and reverse immunoprecipitation assays were used to identify critical interacting protein partners known to drive tumorigenesis. We further correlated our findings to clinical staging of ADC tumor cores by IHC staining.
Results: The expression levels of mtpfeRNA were upregulated in ADC compared to that of squamous cell carcinoma and normal human bronchial epithelial cells. We also noted that blocking the upregulated mtpfeRNA resulted in significant decreases in cell viability in ADC cells. Next, we determined that mtpfeRNA binds to Far Upstream Element Binding Protein 1 (FUBP1). Furthermore, we confirmed that both mtpfeRNA and FUBP1 expression correlated to stages and lymph node metastasis in patients with ADC.
Conclusion: We revealed novel functions of a mtpfeRNA in ADC, providing potential molecules for developing diagnostics and targeted therapy to improve the dismal survival rate of patients with ADC.
Citation Format: Nadege T. Fackche, Yuping Mei, Tomoaki Ito, Matthew Garner, Malcolm Brock. A mitochondrial pfeRNA associates with Far Upstream Element Binding Protein 1 (FUBP1) to promote lung adenocarcinoma tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1822.
Abstract 1826: MALAT1 regulates EGFR translation by KTN1-mediated transcriptomic change in cutaneous squamous cell carcinoma
Authors: Gao Lin , Zhou Liang , Li Shanshan , Ding Zhenhua , Qiu Junying , Hong Malin , Zou Chang 
Published: August 2019

Abstract
Introduction MALAT1 is a member of lncRNAs that has been implicated in breast, cervical, colorectal cancers. However, its role in cutaneous squamous cell carcinoma (cSCC) is not clear. In this study, functional studies using in vitro and in vivo confirmed MALAT1 promotes tumor growth, migration and invasiveness of cSCC. MALAT1 regulates EGFR protein expression but not in RNA level. It shows that identified KTN1 as the key mediator for MALAT1 regulation of EGFR.
Methods Total RNAs from cells were extracted using TRIzol for qRT-PCR. Cells were transfected with MALAT1 ASOs or siKTN1_1, siKTN1_2 and cell proliferation were detected using a cell counting kit as described in the manual. Cells were seeded into chambers for transwell assay. Visible cells were photographed and counted after stained for cell migration and invasiveness assays. Total cell or cSCC tissues were prepared and assayed by western blot as previously described. Bound antibodies were visualised using the Luminated Forte Western HRP substrate. For histochemistry staining, 10 μm tissue sections were fixed for 10min with 4% paraformaldehyde, and then incubated with antibodies. The pictures of stained IHC sections were taken under Leica Fluorescence Microscope. Statistical data were presented as mean values ± stand deviation and considered to reflect significant differences.
Results Our results revealed that MALAT1 was markedly higher expressed in A431, HSC-1 and HSC-5 cSCC cells than in HaCaT keratinocytes. MALAT1 exhibited much higher expression in cSCC primary tumors compared to normal tissues. In addition, KTN1 and EGFR protein were higher expression in cSCC tissues. Significant loss of MALAT1 repressed proliferation, migration, and invasiveness but promoted apoptosis of cSCC cells. Loss of MALAT1 led to the significant downregulation of KTN1 through RNA sequencing assay accompanied with lower EGFR protein expression. However, knockdown of KTN1 had effect on the protein expression of EGFR but no effect on RNA levels. The results implied that MALAT1 may regulate EGFR protein expression through inducing KTN1 mRNA transcription.
Conclusions In this study, we revealed a novel mechanism of cSCC treatment, MALAT1 can transcriptionally activates KTN1, positively regulates EGFR protein expression in cSCC. It may provide a new series of drug target for anti-cSCC therapy.
Citation Format: Lin Gao, Liang Zhou, Shanshan Li, Zhenhua Ding, Junying Qiu, Malin Hong, Chang Zou. MALAT1 regulates EGFR translation by KTN1-mediated transcriptomic change in cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1826.
Abstract 1831: Role of autophagy in lymphangiosarcoma initiation and progression
Authors: Yang Fuchun , Sun Shaogang , Guan Jun-Lin 
Published: August 2019

Abstract
Lymphangiosarcoma is a rare malignant vascular tumor which is formed from aberrant proliferation of endothelial cells (ECs). We previously established a vascular tumor mouse model by conditional knockout of Tsc1 gene in ECs and revealed that hyper-activated mTORC1 and increased VEGF autocrine are required for lymphangiosarcoma development and progression. However, we also found that there are other unknown factors which contribute to vascular tumor development besides mTORC1 hyper-activation. Autophagy has been shown to play an important role in tumor initiation and progression. However, the role of autophagy in mTORC1-dependent vascular tumor development is unclear. In this study, we studied the potential role and mechanism of autophagy in promoting lymphangiosarcoma development. FIP200 (FAK family interacting protein of 200 kDa) was identified as an essential autophagy gene, which was shown to play a key role in breast cancer development and progression. By crossing Tsc1f/f, Scl-Cre mice with Fip200f/f mice, we generated Tsc1/Fip200 double cKO mice. We found that Fip200 deletion blocked lymphangiosarcoma development induced by mTORC1 hyper-activation in mice. We established an immortalized lymphangiosarcoma cell line named Tsc1ΔEC from Tsc1 cKO mice and examined their growth in xenograft transplant models following CRISPR-Cas9 knockout of Fip200, Atg5 or Atg7 in Tsc1ΔEC cells. Our data showed that KO of each of these autophagy genes impaired vascular tumor growth in nude mice. Mechanistically, we found that Fip200 KO suppressed mTORC1 signaling activation under glucose starvation condition. In addition, we found that both Fip200 KO and lipase inhibitor Orlistat treatment in Tsc1ΔEC inhibited mitochondria respiration and decreased ATP content by seahorse assay. We also found that deletion of Fip200, Atg5, Atg7 or LAL in Tsc1ΔEC blocked lipid droplets (LDs) degradation and decreased glycerol release. Collectively, our data suggest that autophagy is required for lymphangiosarcoma initiation and progression through mTORC1 hyper-activation maintenance under stress conditions and supplying energy consumption by regulating lipid metabolism.
Note: This abstract was not presented at the meeting.
Citation Format: Fuchun Yang, Shaogang Sun, Jun-Lin Guan. Role of autophagy in lymphangiosarcoma initiation and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1831.