bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4158: MicroRNA-mediated regulation of Bmi1 expression in gastric and colon cancer cells.
Authors: Sugihara Hidetaka , Ishimoto Takatsugu , Watanabe Masayuki , Baba Hideo 
Published: August 2014

Abstract
Background: MicroRNAs (miRs) target the 3’-untranslated region (3’-UTR) of mRNA and induce translational suppression or mRNA degradation. Bmi1 is a member of the polycomb-repressive complex 1 (PRC1) that has an essential role in maintaining chromatin silencing, and is involved in the self-renewal of neuronal, haematopoietic and intestinal cells through repression of the INK4A-ARF locus. The regulatory mechanism of Bmi1 in cancer cells is still unknown. The aim of this study is to clarify the miR-mediated regulatory mechanism of Bmi1 expression in gastric and colon cancer cells.
Methods and Results: We searched for miRNAs that might regulate Bmi1 using miRBase and selected 64 miRNAs as a candidate. In these miRNAs, we focused miR-30e-3p that was known to be down-regulated in colon, breast and esophageal cancer cells. First, we examined the expression of miR-30e-3p in matched cancer tissue and non-tumor tissue using formalin-fixed paraffin-embedded(FFPE) samples of gastric and colon cancer. We confirmed the expression of miR-30e-3p was significantly lower in cancer tissue than in non-tumor tissue. Next, we measured the expression of miR-30e-3p and Bmi1 by real time PCR and western blotting using gastric and colon cancer cell lines. The endogenous expression of Bmi1 and miR-30e-3p showed inverse correlation in each cell lines. Then we examined the effect of overexpression or down regulation of miR-30e-3p on the expression of Bmi1. The suppression of miR-30e-3p increased Bmi1 expression, and the overexpression of miR-30e-3p decreased Bmi1 expression. Conclusion: Our current study revealed that the expression of Bmi1 was affected by miR-30e-3p in gastric and colon cancer. Mir-30e-3p may be a therapeutic target for the treatment of gastric and colon cancer.
Citation Format: Hidetaka Sugihara, Takatsugu Ishimoto, Masayuki Watanabe, Hideo Baba. MicroRNA-mediated regulation of Bmi1 expression in gastric and colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2013-4158
Abstract 4163: Oncogenic function of miR-196s promote cell invasion through suppression of NME4 to regulate JNK-TIMP1-MMP signaling pathway in head and neck cancer.
Authors: Cheng Ann-Joy , Lu Ya-Ching , Chang Joseph T. 
Published: August 2014

Abstract
Dysregulation of microRNA (miRNA) is associated with malignant transformation, while elucidating the roles remains an ongoing process. In this study, we characterize miR-196 functions in head and neck cancer (HNC). We found that neither miR-196a or miR-196b has an effect on cell growth, only miR-196a plays a role in protection cells from radiation damage, while both miR-196a and miR-196b actively promotes cell migration (1.7- to 2.7-fold) and invasion (2.1- to 2.3-fold), which were supported by the altered expressions of fibronectin and N-cadherin. Mechanistically, miR-196 achieves these functions by targeting and inhibiting the anti-metastatic family member NME4, which is further elucidated as a tumor suppressor to repress JNK protein phosphorylation, leading to TIMP1 inhibition and MMP1/9 activation. Furthermore, both miR-196a and miR-196b was significantly over-expressed in the cancer tissues compared to the normal counterparts, with approximately 60 and 10 fold elevations respectively in average. Over-expression of miR-196 was correlated to lymph node metastasis and poor survival. In summary, our findings define miR-196 as a crucial oncomir in HNC which acts at least in part, through NME4-pJNK-TIMP-MMP signaling pathway to promote cell invasion and cellular transformation.
Citation Format: Ann-Joy Cheng, Ya-Ching Lu, Joseph T. Chang. Oncogenic function of miR-196s promote cell invasion through suppression of NME4 to regulate JNK-TIMP1-MMP signaling pathway in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4163. doi:10.1158/1538-7445.AM2013-4163
Abstract 4178: The role of miR-1 in RAS mutation prostate cancer metastasis.
Authors: Liu Yen-Nien , Yin Juan Juan , Barrett Ben , Sheppard-Tillman Heather , Casey Orla , Kelly Kathy 
Published: August 2014

Abstract
Several mechanisms have been suggested to impact prostate cancer progression, including mutation of Ras, either genetically or epigenetically during prostate cancer metastasis. MicroRNAs (miRs) are involved in embryonic development and prostate cancer metastasis. MiR-1 expression has been found to be downregulated in prostate cancer clinical cases relative to normal prostate tissue. It is not clear how miR-1 expression relates to Ras mutation in prostate cancer metastasis. Identifying the regulatory mechanisms of miR-1 in relation to Ras signaling will define roles of the miR-1 regulatory pathway in prostate metastatic processes. To investigate the contribution of this miRNA in Ras signaling pathway, we are using lentiviral expression systems to enhance miR-1 expression in a metastatic human prostate cancer cell line. Following confirmation of miR-1 over-expression, we have found that the metastatic prostate cancer cell line DU145 with RasV12G37 mutant displayed reduced metastasis and tumor growth ability in vivo, and decreased expression of a miR-1 target gene and Ras-related gene expression in vitro. We hypothesize that upon activation of Ras signaling genes, reduced expression of miR-1 is required for prostate cancer metastasis. Our results will provide evidence to show how miR-1 regulates Ras signaling genes in prostate cancer progression.
Citation Format: Yen-Nien Liu, Juan Juan Yin, Ben Barrett, Heather Sheppard-Tillman, Orla Casey, Kathy Kelly. The role of miR-1 in RAS mutation prostate cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4178. doi:10.1158/1538-7445.AM2013-4178
Abstract 4183: MicroRNA-7 targeting PSME3 inhibits the growth of non-small cell lung cancer.
Authors: Chu Yiwei 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are a family of small non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis..In this study, we found that the expression of miR-7 was downregulated not only in cell lines, but also in human NSCLC tissues compared to the matched adjacent tissues, which exhibited positive correlation with tumor volume.Restoration of its expression through miR-7 mimics in NSCLC cell lines including A549 and H1299 cells inhibited cell proliferation, colony formation, and cell cycle progression in vitro. More importantly, the tumorigenicity in nude mice was reduced after administration of miR-7 in vivo, strongly indicating that miR-7 is a main tumor suppressor miRNA in NSCLC. In advance, through a series of analysis derived from bioinformatics prediction, western blot and luciferase assay, we identified a novel target of miR-7, PSME3 (a proteasome activator) to be enrolled in the regulation with tumor. Expression of PSME3 in NSCLC tumor samples was significantly upregulated compared to adjacent non-tumor tissues, exhibiting a strong inverse relation with that of miR-7. In addition, knockdown of PSME3 gene induced similar effects to overexpression of miR-7 in NSCLC cells. All these findings strongly imply that the overexpression of PSME3 resulted from miR-7 downexpression in NSCLC plays an important role in promoting cancer cell progress, and consequently results in NSCLC growth. Thus, strategies targeting PSME3 and/or miR-7 may be the promising molecular therapy in NSCLC treatment.
Citation Format: Yiwei Chu. MicroRNA-7 targeting PSME3 inhibits the growth of non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4183. doi:10.1158/1538-7445.AM2013-4183
Abstract 4185: miR-129 is a potential tumor suppressor in colorectal cancer by regulating apoptosis and modulating fluropyrimidine based chemosensitivity.
Authors: Karaayvaz Mihriban , Zhai Haiyan , Ju Jingfang 
Published: August 2014

Abstract
Resistance to fluoropyrimidine based chemotherapy is the major reason for the failure of treating advanced colorectal cancer. The lack of ability for tumor cells to undergo apoptosis after genotoxic stress is the key contributor to such intrinsic mechanism. Mounting evidence has demonstrated that non-coding microRNAs (miRNAs) are crucial regulators of gene expression, in particular, under acute stress. However, there is still very limited knowledge about the role of miRNAs in apoptosis. In this study, we discovered a novel mechanism mediated by miR-129 directly inducing apoptosis by suppressing a key anti-apoptotic protein Bcl-2. Ectopic expression of miR-129 promotes apoptosis, inhibits cell proliferation and causes G2-cell-cycle arrest in colon cancer cells in vitro. The intrinsic apoptotic pathway triggered by miR-129 is activated by cleaving caspase-9 and caspase-3. The expression of miR-129 is very significantly down-regulated in colorectal cancer tissue specimens compared with the paired normal control samples (p&lt;0.00001). More importantly, we demonstrated that miR-129 functions synergistically with 5-fluorouracil (5-FU) in vitro and in vivo to enhance 5-FU cytotoxicity. These results suggest that miR-129 is a major regulator of apoptosis in colorectal cancer. Therefore, miR-129 may be a potential tumor suppressor in colorectal cancer and a novel candidate for developing miR-129 based therapeutic strategies.
Citation Format: Mihriban Karaayvaz, Haiyan Zhai, Jingfang Ju. miR-129 is a potential tumor suppressor in colorectal cancer by regulating apoptosis and modulating fluropyrimidine based chemosensitivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4185. doi:10.1158/1538-7445.AM2013-4185
Abstract 419: A comparison between the OV100 and Maestro fluorescence imaging systems for noninvasive detection of metastasis.
Authors: Zhang Yong , Zhang Nan , Hoffman Robert M. , Zhao Ming 
Published: August 2014

Abstract
The OV100 (Olympus Corp.), and Maestro (Perkin-Elmer Inc.), were compared for imaging metastasis in orthotopic lung, liver, pancreas and colon nude mouse tumor models expressing RFP. Non-invasive images of tumor-bearing mice indicated that the Maestro systems outperformed the OV100 for macro imaging. Tumors could be detected earlier with the Maestro system than with the OV100. By separating skin and food autofluorescence, the Maestro provides a high-contrast image. The Maestro can produce a composite image of five unmixed components and detects tumors deeper than the OV100. The Maestro can also detect more color signals simultaneously. However, the OV100 has higher resolution and even a single cell can be imaged, for example via a skin-flap. The results of this study suggest that the two instruments are complimentary.
Citation Format: Yong Zhang, Nan Zhang, Robert M. Hoffman, Ming Zhao. A comparison between the OV100 and Maestro fluorescence imaging systems for noninvasive detection of metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 419. doi:10.1158/1538-7445.AM2013-419
Abstract 4195: Identification of dysregulated miRs and its target genes in head and neck cancer.
Authors: Kuo Yi-Zih , Huang Yun-Chu , Chen Yuh-Ling , Lo Hung-I , Tsai Sen-Tien , Chiang Chi-Wu , Wu Li-Wha 
Published: August 2014

Abstract
Oral cancer is a subtype of head and neck cancer, the eighth common cancer type in the world. MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional level by degrading target messenger RNA or repressing their translation. The deregulation of certain microRNAs has been associated with the progression and metastasis of various cancer types. A total of 133 miRs were dysregulated in oral cancer cells when compared with normal oral keratinocytes by using microRNA microarray hybridization. Among them, miR-22, often silenced in breast cancer, colon cancer, and multiple myeloma, is downregulated and least known in oral carcinogenesis. In this study, we confirmed the down-regulation of miR-22 in the majority of oral cell lines and 70 % of the tested clinical specimens, as measured by real-time PCR. Both gain-of-function and loss-of-function experiments showed that increased miR-22 expression significantly reduced oral cancer cell migration and invasion, whereas decreased miR-22 expression dramatically enhanced cell migration and invasion. Snail, a transcription factor that promotes cell invasion and tumor metastasis, was predicted to be a target of miR-22. The prediction was validated by the inverse correlation of miR-22 and snail protein, and the luciferase reporter assay bearing 3’- translated region derived from snail. Silencing snail expression by using shRNA recapitulated the anti-metastatic function of miR-22, whereas restored snail expression attenuated the function of miR-22 in oral cancer cells. Together, these results suggest that miR-22 may act as a tumor suppressor through decreasing snail expression in oral cancer and thus be used as a therapeutic target to block oral cancer metastasis.
Citation Format: Yi-Zih Kuo, Yun-Chu Huang, Yuh-Ling Chen, Hung-I Lo, Sen-Tien Tsai, Chi-Wu Chiang, Li-Wha Wu. Identification of dysregulated miRs and its target genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4195. doi:10.1158/1538-7445.AM2013-4195
Abstract 4202: Oncogenic microRNA-31 as prognostic potential biomarker in histologically negative surgical margins of head and neck cancer patients.
Authors: Horst Maria Aderuza , Carvalho Ana Carolina , Maia Danielle Campelo , Aymberé Bello Juliana , Kowalski Luiz Paulo , Carvalho Andre Lopes , Vettore Andre Luiz 
Published: August 2014

Abstract
The development of locoregional recurrence is the main reason for treatment failure in head and neck squamous cell carcinomas (HNSCC) and the remaining of tumor cells in surgical margins is associated with recurrence. Surgical margins are considered negative based on histologic assessment of the pathological specimen. However, this method lacks sensitivity in identifying cells that already started malignant transformation but have not yet developed a pathologic phenotype. We investigated the usefulness of assessing the expression of microRNA-31 for the detection of molecular alterations in histologically negative surgical margins (HNSM) and determine the correlation of these tumor-related alterations with clinical and prognostic parameters. MicroRNAs are endogenously expressed non-coding RNAs that have important biological and pathological functions. The microRNA-31 was found markedly upregulated in different malignancies, including HNSCC. The microRNA-31 expression was determined by qRT-PCR in HNSCC (n=19), HNSM (n=37) and normal mucosa (n=10). According to our results, 76% of tumor samples and 30% of the HNSM specimens were positive for microRNA-31 overexpression. Moreover, the overexpression of this microRNA in the HNSM was associated with perineural invasion (p &lt; 0.05 Fisher's exact tests) and showed a tendency to correlates with poor disease-free survival (p &lt; 0,09 log-rank).
These findings demonstrate that the overexpression of microRNA-31 in histologically negative surgical margins is a frequent event. The use of qRT-PCR may be an useful tool in detecting actually negative HNSCC surgical margins and the overexpression of microRNA-31 in these margins could be helpful in the identification of patients with worst outcome.
Supported by Fapesp (Grant 2011/01919-2).
Citation Format: Maria Aderuza Horst, Ana Carolina Carvalho, Danielle Campelo Maia, Juliana Aymberé Bello, Luiz Paulo Kowalski, Andre Lopes Carvalho, Andre Luiz Vettore. Oncogenic microRNA-31 as prognostic potential biomarker in histologically negative surgical margins of head and neck cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4202. doi:10.1158/1538-7445.AM2013-4202
Abstract 4206: Impact of nuclear telomere architecture in the transition of myelodysplastic syndromes to acute myeloid leukemias.
Authors: Gadji Macoura , de Oliveira Fábio Morato , Mai Sabine 
Published: August 2014

Abstract
Myelodysplastic Syndromes (MDS) are a group of disorders characterized by cytopenias, with a propensity for evolution into Acute Myeloid Leukemias (AML). This transformation is driven by genomic instability and epigenetic events. However, how genomic instability occurs in this disease remains unknown. Telomere dysfunction might be the generator of genomic instability leading to cytopenias and disease progression. Despite several studies demonstrating the role of telomere dysfunction in the occurrence of hematopoietic malignancies, little is known about their role in the evolution of MDS to AML/MDS. Our preliminary data allowed us to define three-dimensional nuclear telomeric profiles on the basis of telomere numbers, telomeric aggregates, telomere signal intensities, nuclear volumes, and nuclear telomere distribution. Using these parameters, we blindly subdivided the MDS patients into nine subgroups and the AML patients into six subgroups. We showed distinct telomeric profiles specific to patients with MDS, AML, and suggested for the first time a chronological and evolutionary process of telomere dysfunction in both diseases and the transformation of MDS to AML. To validate the clinical significance of 3D telomere profiling of MDS-patients and AML-patients, we are studying new patient cohorts and patients progressing from MDS to AML over time. Such a longitudinal study will allow for precise 3D telomeric profiling during disease progression. Since transformation of MDS to AML can occur over a long period of time, we are also studying disease progression from MDS to AML using a mouse model (C57BL/6-Tg(Vava1-NUP98/HOXD13)G2Apla/J). These mice will transform their MDS-disease to AML disease in a time period of in between 4-14 months. Therefore, we are following the mice monthly up to 14 months. Our study will allow us to gain an understanding of the 3D telomeric signatures that predict and accompany the transition of MDS to AML. In addition, we will define the molecular profiles at disease transition to improve, once validated, treatment strategies for patients with MDS/AML.
Citation Format: Macoura Gadji, Fábio Morato de Oliveira, Sabine Mai. Impact of nuclear telomere architecture in the transition of myelodysplastic syndromes to acute myeloid leukemias. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4206. doi:10.1158/1538-7445.AM2013-4206
Abstract 4210: An osteopontin promoter polymorphism is associated with aggressiveness in breast cancer.
Authors: Weber Georg F. , Ramchandani Divya 
Published: August 2014

Abstract
Background: Like cancer initiation, cancer progression and metastasis are genetically programmed. However, unlike oncogenes metastasis genes are deregulated in cancer by aberrant expression or splicing. We have previously described splicing of the metastasis gene osteopontin in cancers. Here we have analyzed polymorphic sites in the osteopontin promoter as potential contributors to aberrant expression in breast cancers.
Methods: This study comprised 241 breast cancer specimens, for 111 of which DNA from normal surrounding tissue was available, and 65 healthy breast samples. One probe set tested the polymorphic promoter sites -66, -443, -1748 and -1776. For comparison, we also investigated non-synonymous DNA sequence variations in the coding region positions 305, 367, 794 and 1025.
Results: The polymorphic sites in positions -66 and 305 were not in Hardy-Weinberg equilibrium and hence were not included in further analyses. The polymorphic site in position -443 of the promoter was associated with tumor grade. Expectedly, there was no association of the promoter SNPs with tumor stage or with in situ carcinoma versus cancer, as stage and early transformation are determined by the sampling time more than by tumor genetics. In a subset of samples, osteopontin expression levels had previously been obtained. The allelic distribution in positions -443 and -1748 was distinct between high and low expressors, confirming the importance of promoter SNPs. These two sites also form a haplotype. Osteopontin expression has been associated with breast cancer progression, regardless of the histologic subtype of the cancer. Remarkably, the polymorphic site at -443, but not -1748 or -1776, showed differences between ER positive and ER negative breast cancers and between PR positive and PR negative breast cancers, but there was no association with HER2 status. In five cases, the genotype of the tumor was different from the genotype of the host, implying the possibility of somatic mutations in the osteopontin promoter that may affect expression. The polymorphic sites in positions 367, 794, and 1025 showed one homozygous genotype for all specimens in this study.
Conclusion: Our results show that the osteopontin promoter SNPs -443 (rs11730582) and -1748 (rs2728127) are important for gene expression and tumor aggressiveness.
Citation Format: Georg F. Weber, Divya Ramchandani. An osteopontin promoter polymorphism is associated with aggressiveness in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4210. doi:10.1158/1538-7445.AM2013-4210