bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3755: Dlx4os: a lncRNA associated with malignant melanocyte transformation
Authors: Ayub Ana Luísa P. , Azevedo Hatylas , Pessoa Diogo , Sejour Leinal , Vlachos Ioannis , Reis Eduardo M. , Slack Frank J. , Jasiulionis Miriam G. 
Published: April 2023

Abstract
It is estimated that more than 90% of the human genome is transcribed into non-coding RNAs (ncRNA). It has been demonstrated that ncRNAs have an important role in biological processes such as proliferation, differentiation, and cell migration. Changes in their expression have been associated with several diseases, including cancer. Melanoma is one of the most aggressive types of cancer, with high probability of metastasis and an unfavorable response to therapies. Our lab has developed an in vitro melanoma progression model, which was established by exposing nontumorigenic melanocytes (melan-a) to sustained stress conditions (cycles of adhesion blockage), sequentially generating different cell lines (i.e., 4C, premalignant melanocytes; 4C11-, non-metastatic melanoma cells; and 4C11+, metastatic melanoma cells), in which each cell line represents a distinct stage of tumor progression. Previous RNA sequencing data comparing these 4 cell lines identified a total of 3404 long non-coding transcripts which displayed differential expression (DE) levels when comparing two or more cell lines. We have clustered 531 of them into three distinct signatures: malignancy, epithelial-to-mesenchymal transition (EMT), or metastasis, according to their expression profiles. We also analyzed the neighboring genes of those lncRNAs, as it is known that lncRNAs might regulate gene expression in cis. We identified the lncRNA Dlx4os, highly expressed in undifferentiated and mesenchymal-like 4C and 4C11- cells, and 6 neighboring genes whose expression correlate to the EMT signature and overall survival in human melanoma patients. Among these genes we found Dlx4, which shares the same promoter site with Dlx4os and whose expression correlates to a poor prognosis. We silenced Dlx4os in the 4C11- cells through interference RNA technology. The downregulation of Dlx4os led to expression changes in EMT-related genes, such as Snail1, Sox10 and Mitf, indicating that it might play a role in EMT. Dlx4os downregulation also inhibited cell migration in vitro and tumorigenesis in vivo. These results overall indicate a role of Dlx4os in melanocyte malignant transformation.
Citation Format: Ana Luísa P. Ayub, Hatylas Azevedo, Diogo Pessoa, Leinal Sejour, Ioannis Vlachos, Eduardo M. Reis, Frank J. Slack, Miriam G. Jasiulionis. Dlx4os: a lncRNA associated with malignant melanocyte transformation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3755.
Abstract 3756: miR-145 and its gene targets as therapeutic target and prognostic biomarkers for non-small cell lung cancer
Authors: Cho William C. , Wong Chi F. , Li Leo K. , Fong Alvin H. 
Published: April 2023

Abstract
Introduction: Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and it could inhibit cell proliferation in transfected NSCLC cells. This study aimed to investigate the potential anticancer effect and tumor suppressive function of miR-145, to identify its gene targets, as well as to assess the role of its gene targets as prognostic biomarkers for NSCLC patients.
Materials and Methods: Cell proliferation, transwell migration, and invasion assays were performed on three miR-145 mimics transfected NSCLC cells. The effect of miR-145 in the cell cycle in vitro was assessed by flow cytometry analysis. In vivo transfection of miR-145 was performed to examine the cancer growth in eight BALB/c nude mice. Luciferase reporter assay was used to identify the gene targets. To reveal the role of the identified gene targets in patient survival, the clinical data of 500 lung adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database was used for Kaplan-Meier survival analysis.
Results: Upregulation of miR-145 significantly inhibited proliferation, migration, and invasion in NSCLC cells in vitro. Flow cytometry analysis revealed that the transfection of miR-145 into NSCLC cells did not show any effect in the cell cycle. After 37 days, transfection of miR-145 showed a reduction in tumor size (49% smaller) and tumor weight (57% lighter) than mimic negative in vivo. MicroRNA target prediction database miRTarBase and luciferase reporter assays identified GOLM1 and RTKN as the direct targets of miR-145. TCGA survival analysis found that the high expressions of GOLM1 (p &lt; 0.0001) and RTKN (p &lt; 0.0045) were significantly correlated with poor overall survival in lung adenocarcinoma patients.
Conclusion: Our results revealed that miR-145 inhibited proliferation, migration, and invasion, but did not affect cell cycle regulation in NSCLC. It also caused a reduction in tumor growth and weight. Most importantly, we identified two direct targets (GOLM1 and RTKN) of miR-145, in which RTKN was first identified as a miR-145 target in NSCLC. Moreover, both GOLM1 and RTKN play an imperative role in patients’ overall survival. Taken together, our findings suggest that miR-145 may serve as a molecular therapeutic target for NSCLC, and its gene targets GOLM1 and RTKN may serve as prognostic biomarkers. Their potential clinical applications warrant further investigation.
Citation Format: William C. Cho, Chi F. Wong, Leo K. Li, Alvin H. Fong. miR-145 and its gene targets as therapeutic target and prognostic biomarkers for non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3756.
Abstract 3763: microRNAs associated with metastatic potential in salivary gland mucoepidermoid carcinoma
Authors: Trevizani Maria Eduarda S. , Oliveira Katia K. , Marchi Fabio A. , Bizinelli Daniela , Mariano Fernanda V. , Nagano Cibele P. , Costa Felipe A. , Pinto Clóvis A. , Kowalski Luiz P. , Lourenço Silvia V. , Coutinho-Camillo Cláudia M. 
Published: April 2023

Abstract
Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Metastatic spread occurs in up to 80% of high-grade tumors and it is a strong predictor of poor outcome, however, the mechanisms underlying this process are largely unknown. Large-scale microRNA expression profiling studies of human cancers have demonstrated that dysregulation of miRNA is frequently associated with many cancer types. The aim of this study was to investigate the microRNA profile in metastatic versus non-metastatic MECs. Using Real Time RT-PCR (qPCR) we have analyzed the expression of 384 miRNAs and controls in 4 non-metastatic MECs, 3 MECs with lymph node metastasis, 3 MECs with distant metastasis, and 2 non-neoplastic human salivary gland samples. The microRNA profile was able to discriminate between non-neoplastic and tumor samples and between metastatic and non-metastatic tumors. Considering non-neoplastic samples and non-metastatic MECs, 12 microRNAs were differentially expressed. The non-neoplastic versus lymph node metastasis MEC analysis demonstrated that 10 microRNAs were differentially expressed. Considering non-neoplastic versus distant metastasis MECs, 3 microRNAs were differentially expressed: 1 down-regulated and 2 up-regulated. Comparing non-metastatic MECs versus lymph node metastasis MECs we observed 17 up-regulated microRNAs. Considering non-metastatic MECs versus distant metastasis MECs, 2 microRNAs were up-regulated. One microRNA is differentially expressed between lymph node metastasis MECs and distant metastasis MECs. Our results suggest that microRNA profiles could discriminate the metastatic potential of salivary MECs and might be helpful in diagnostic and prognostic evaluation of patients.
Citation Format: Maria Eduarda S. Trevizani, Katia K. Oliveira, Fabio A. Marchi, Daniela Bizinelli, Fernanda V. Mariano, Cibele P. Nagano, Felipe A. Costa, Clóvis A. Pinto, Luiz P. Kowalski, Silvia V. Lourenço, Cláudia M. Coutinho-Camillo. microRNAs associated with metastatic potential in salivary gland mucoepidermoid carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3763.
Abstract 3770: Hypoxia-induced circular RNAcircSFMBT2 inhibits tumor malignancy in breast cancer cells
Authors: Liu Chia-Ming , Ke Yi-Chun , Lai Liang-Chuan 
Published: April 2023

Abstract
Breast cancer is the most prevalent cancer among women, and the second major cause of cancer-related deaths in women worldwide. The hypoxic microenvironment of solid tumors is formed in the progress of carcinogenesis, which leads to more malignant and treatment resistance. Recently, circular RNAs (circRNA), a kind of noncoding RNA, were discovered to influence the progress of tumorigenesis, and were induced under hypoxia. However, the regulation and functions of hypoxia-induced circRNA in breast cancer remain unclear. Therefore, the purpose of this study is to identify the regulatory mechanism and its function of a hypoxia-induced circRNAs, circSFMBT2, in breast cancer cells. Firstly, hypoxia-responsive circRNA candidates in breast cancer MCF-7 cells under different oxygen concentrations were identified by RNA-sequencing. Among the differentially expressed circRNAs, circSFMBT2 was chosen for further experiments. The up-regulation of circSFMBT2 under hypoxia was validated by quantitative RT-PCR. The functional assays showed that overexpression of circSFMBT2 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Next, in order to investigate the regulatory mechanisms of circSFMBT2, nuclear and cytoplasm fractionation was performed. The results showed circSFMBT2 predominantly localized in the cytoplasm, indicating that the regulatory mechanism of circSFMBT2 might be via interaction with microRNA or RNA-binding proteins (RBP). In order to identify the RBPs, bioinformatic tools, RBPDB, ATtRACT, and RBPmap, were first used to predict the candidate RBPs and validated by RNA pulldown assays. The RNA-binding protein PABPC1 was proved to bind with circSFMBT2. On the other hand, the potential sponging microRNAs were predicted by ENCORI and miRDB, followed by qRT-PCR. No miRNAs were shown to bind with circSFMBT2. Lastly, the functions of circSFMBT2 were explored by identifying its downstream genes using Affymetrix microarrays. The top 10 differentially expressed genes were chosen for validation by quantitative RT-PCR. However, no genes showed significant changes in cells overexpressing circSFMBT2, implying the regulation of circSFMBT2 might not be at the transcriptional level. In summary, circSFMBT2 was able to inhibit the cellular function of breast cancer and bind to PABPC1. With a deeper understanding of the regulatory mechanisms of circSFMBT2, we hope to develop a novel treatment regime for breast cancer.
Citation Format: Chia-Ming Liu, Yi-Chun Ke, Liang-Chuan Lai. Hypoxia-induced circular RNAcircSFMBT2 inhibits tumor malignancy in breast cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3770.
Abstract 3814: In CLL the U1 snRNA driver mutation alters splicing in multiple genes and pathways
Authors: Senff-Ribeiro Andrea , Almodaresi Fatemeh , Trinh Quang , Shuai Shimin , Spaner David , Puente Xose S. , Campo Elias , Stein Lincoln D. 
Published: April 2023

Abstract
5-10% of patients with the IGHV wild type form of chronic lymphocytic leukemia (CLL) carry a g.3A&gt;C driver mutation in the U1 small nuclear RNA (snRNA). We investigatedthe patterns of mis-splicing and their pathway consequences in three U1-mutant CLL cellline models using long read sequencing in order to better understand the mechanisms ofoncogenicity in tumors carrying this mutation. CLL cell lines (HG3, JVM3 and MEC1) expressing the U1 mutation and their wild-type counterparts were submitted to Oxford Nanopore sequencing to generate full-length RNA transcripts. This transcriptomic datawas evaluated, together with previously obtained short-read data. The g.3A&gt;C mutation occurs at a specific location of the U1 snRNA, a core component of the eukaryotic spliceosome, and acts by altering the 5' splice site (5'SS) recognition sequence to cause consistent patterns of mis-splicing. Long read analysis identified multiple instances of intron retention and suppression of exon skipping, and in silico translation of these mis-splicing events predicted stop-gain and other loss of function mutations in several expressed genes, as well as widespread changes in gene expression levels. We performed a pathway overrepresentation analysis of the altered gene expression patterns in the mutant cells using the Reactome knowledgebase and identified an enrichment in the processes of translation, non-sense mediated decay (NMD) and immune signaling, including interferon signaling. In particular, there was a marked down-regulation of genes related to ribosomal assembly and the translational machinery. A more comprehensiveanalysis of the U1 mutation phenotype in CLL may accelerate the development ofbetter therapeutic and diagnostic approaches in patients.
Citation Format: Andrea Senff-Ribeiro, Fatemeh Almodaresi, Quang Trinh, Shimin Shuai, David Spaner, Xose S. Puente, Elias Campo, Lincoln D. Stein. In CLL the U1 snRNA driver mutation alters splicing in multiple genes and pathways. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3814.
Abstract 3819: Naringin nanoparticles inhibit metastasis of lung cancer through TGF-β1-smad2/3 signaling pathway
Authors: Chen Wen 
Published: April 2023

Abstract
Lung cancer causes high mortality due to its high metastasis. Naringin is a naturally occurring flavonoid that is widely found in the various citrus fruits. Naringin is known to have several therapeutic effects including anticancer, anti-pulmonary fibrosis, antimicrobial, anti-inflammatory. However, low bioavailability and solubility of naringin limit its application. This project designed a thermosensitive naringin nanoparticle to investigate whether it might inhibit metastasis of lung cancer by inhibiting TGF-β1-smad2/3 signaling pathway. Cells were treated with various concentrations of naringin nanoparticles and unwrapped naringin for 48 hours. Naringin nanoparticles of 100µmol/L showed obvious inhibitory effect on the larger wound surface of cultured human cancer cells. Westerm blot was used to detect the expression of P-Smad2, Smad2,and α-SMA in A549 cells. The results showed that naringin significantly reduced the expression of EMT-related protein α-SMA in A549 cells in a concentration-dependent manner. Naringin nanoparticles can reverse the EMT process. naringin nanoparticles can inhibit the expression of P-Smad2 protein in A549 cells, which may play a role in inhibiting lung cancer through TGF-β1/Smad signaling pathway.The animal experiment was performed. The mice were given various concentrations of naringin nanoparticles and unwrapped naringin by IV. the protein expression levels of α-SMA, TGF-β1 and P-Smad3 in mice lung tissue were detected by immunohistochemistry. The results showed that naringin nanoparticles 50um/ml,0.2mL/day/time had significant effect on the inhibition of lung cancer tissue migration, and the different doses of naringin nanoparticles showed a certain dose-dependent trend. The expression of TGF-β1 and P-Smad3 in mice treated with naringin nanoparticles was significantly decreased, suggesting that naringin nanoparticles could inhibit the migration of lung cancer cells by inhibiting TGF-β1/Smad pathway.
Citation Format: Wen Chen. Naringin nanoparticles inhibit metastasis of lung cancer through TGF-β1-smad2/3 signaling pathway. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3819.
Abstract 3820: Changes in the transcriptome of a triple negative breast cancer cell line following treatment with a water-soluble extract from the leaves of the indigenous Southern African plant Tulbaghia violacea
Authors: Dlamini Zodwa , Hull Rodney , Alouna Mohammed , Penny Clement 
Published: April 2023

Abstract
Triple negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases. And is defined by the absence of oestrogen, progesterone, and human epidermal growth factor 2 receptors. This makes it difficult to treat and leads to a low five-year survival rate. In South Africa a large percentage of the population still relies on traditional medicine based on the use of medicinal plants. One of these plants, African garlic (Tulbaghia violacea), that has been used to treat symptoms similar to that observed in cancer. However, the usefulness of these treatments has yet to be clinically proven. Previous studies have revealed that the water-soluble extract from the leaves of T. violacea had anticancer activity against a TNBC cell line. In order to identify the signalling pathways involved in this anti-cancer activity whole transcriptome sequencing was performed using RNA extracted from both TNBC and normal breast cells before and after treatment with the water-soluble T. violacea extract. Paired end sequencing was performed at a depth of 10 million bases for 300 cycles. Data analysis was performed using the Galaxy platform/Sequencing results led us to perform an antibody array assay for proteins involved in the receptor tyrosine kinase pathway. In line with the increased levels of apoptosis previously observed following treatment of the TNBC cell line with the extract, there was an increase in the transcription of genes associated with apoptosis. Decreases were observed in the transcription of genes involved in growth receptor signalling, angiogenesis, and cancer related pathways such as the Wnt, Notch and the PI3K pathway. This work highlights the pathways affected by compounds present within a water-soluble extract of the leaves of T, violacea. Combined with the results of our [previous work, this indicates that the compounds isolated from T, violacea could serve as lead compounds for the development of future therapeutic treatments for TNBC.
Citation Format: Zodwa Dlamini, Rodney Hull, Mohammed Alouna, Clement Penny. Changes in the transcriptome of a triple negative breast cancer cell line following treatment with a water-soluble extract from the leaves of the indigenous Southern African plant Tulbaghia violacea. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3820.
Abstract 3828: Herbal extracts from lycii radicis corex and achyranthes japonica prevent multiple myeloma progression
Authors: Mehdi Syed Hassan , Lee Sun-OK , Huh Dam , Yoon Donghoon 
Published: April 2023

Abstract
Multiple Myeloma (MM) is a plasma cell malignancy that, despite advances in treatment, remains incurable. In over 90% of MM patients, aberrant bone remodeling occurs and results in osteolytic lesions. Korean traditional medicine has a long-standing interest in healthy foods to enhance the immune system, energy-boost, and Yin-and-Yang balance. Traditional medicine has used herbal extracts (HE) from natural plants with fewer side effects and long-term treatment tolerance. In earlier studies, lycii radices cortex (LRC) and achyranthes japonica (AJ) containing HE have demonstrated the ability to enhance cell growth and mineralization of osteoblast cells while also inhibiting osteoclast differentiation. The current study investigated the effects of LRC+AJ containing HE on murine 5TGM1 MM-bearing mice.This HE significantly increased the mouse survivals of both Treatment before Transplant (TbT) and Treatment after Transplant (TaT) groups with median survivals of undetermined and 52.5 days, respectively, while MM control had a median survival of 42 days. The Mantel-Cox test found that TbT and TaT mice were significantly different from the control group (P=0.0014 and 0.0182, respectively). In histomorphometric analysis, the spines were scanned by micro-CT and revealed that TbT and TaT groups had significantly increased bone volume over total volume (BV/TV) than control. To see if HE affects cell growth of myeloma cells and osteoblast cells, we further investigated the HE on preosteoblast cell line MC3T3-E1, mouse MM cell line 5TGM1-Luc, and human MM cell line U-266. Cells were treated with HE, and viability was assessed at 48 and 96 hours post-treatment. Remarkably, LRC+AJ containing HE increased MC3T3-E1 cell growth while it decreased 5TGM1 and U-266 cell viability. In addition, we found the DAP3G in HE used in this study.Our results demonstrated that LRC+AJ HE prevents MM and promotes bone formation in 5TGM1 engrafted NSG mice. We also found that LRC+AJ HE suppresses myeloma cell growth and enhances osteoblast cell survival. Although it is yet to be defined, a correlation of osteoblast activity and myeloma cell inhibition suggests a possible connection of these events to prevent MM progression.
Citation Format: Syed Hassan Mehdi, Sun-OK Lee, Dam Huh, Donghoon Yoon. Herbal extracts from lycii radicis corex and achyranthes japonica prevent multiple myeloma progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3828.