bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2066: Role of miR-182/miR-96 cluster in prostatic zinc homeostasis
Authors: Khramtsova Ekaterina A. , Vaishnav Avani , Arva Nicoleta , Antonio Angeline , Kajdacsy-Balla Andre , Nonn Larisa 
Published: February 2011

Abstract
Zinc has been shown to have a defensive action against the development of prostate cancer (PCa). Zinc is an essential element that is required for the activity of more than 300 enzymes, structure of proteins, and control of genetic expression. It plays an important role in cellular processes such as cell division, growth, differentiation, development, aging, and synthesis and repair of DNA, RNA, and protein. Prostatic secretary epithelial cells accumulate large amounts of zinc and have a high expression of human Zinc transporter 1 (hZIP1), the major zinc transporter in the prostate. PCa tissue exhibits lower levels of zinc and hZIP1 compared with surrounding normal-appearing areas. Furthermore, compared to Caucasian men, the prostates of African American men, a population with a disproportionately high risk of developing PCa, have decreased zinc and hZIP1. Previously, we examined several miRNAs in formalin-fixed paraffin-embedded prostate tissue from African American and Caucasian patients, of which miR-182/96 levels were higher in PCa samples and had inverse correlation with hZIP1 mRNA in Caucasian patients (Spearman rho = −0.77, p=0.009). No correlation between hZIP1 and miR-182 was found in the African-American specimens, suggesting a different mechanism for hZIP1 regulation in African-Americans. Based on previous studies, we hypothesize that miR-182/96 cluster is responsible for regulation of hZIP1 levels in PCa and prostate tissue. In this study, we examined the relationship between the levels of miR-182/96 and hZIP1 in more detail using cell culture models. We observed an inverse correlation between hZIP1 and miR-182 levels in several prostate cell cultures; primary normal epithelial cells, normal stromal cells, and prostate cancer cells (PC3 and LNCaP). MiR-182 is transcribed in a cluster with miR-96 and the miRNAs have an overlapping mRNA target sequence. As expected, miR-96 expression was identical to that of miR-182, thus also inversely correlated with hZIP1 in prostate cell cultures. Overexpression of miR-182 in both normal and LNCaP cells decreased hZIP1 mRNA levels, further implicating miR-182 as a regulator of zinc transport. Ongoing experiments focus on validating the two putative miR-182/96 binding sites in the 3′UTR of hZIP1 and the effect of miR-182 and miR-96 overexpression on zinc transport. Our results may establish a role for miR-182 in prostatic zinc homeostasis. Because zinc levels are linked to PCa risk, these miRNAs may be useful as a prognostic or diagnostic marker in prostate biopsies to identify patients with high risk of PCa recurrence and for identifying individuals for zinc replacement.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2066.
Abstract 2067: Effects of microRNA-34a on brain tumor cells and glioblastoma stem cells
Authors: Guessous Fadila , Zhang Ying , Catania Alessia , Li Yunqing , Kofman Alexander , Kefas Benjamin , Schiff David , Purow Benjamin , Abounader Roger 
Published: February 2011

Abstract
Glioblastoma and medulloblastoma are the most common malignant brain tumors in adults and children, respectively. microRNAs are deregulated in different types of cancer including brain tumors. We previously found that microRNA-34a (miR-34a) inhibits brain tumor growth by targeting multiple oncogenes. We showed that miR-34a is downregulated in glioblastoma tumors. miR-34a down-regulated c-Met in human glioblastoma and medulloblastoma cells and Notch-1, Notch-2, and CDK6 protein expressions in glioblastoma cells. miR-34a expression inhibited c-Met reporter activities in glioblastoma and medulloblastoma cells and Notch-1 and Notch-2 3′-UTR reporter activities in glioblastoma cells and stem cells. miR-34a strongly inhibited cell proliferation, cell cycle progression, cell survival, and cell invasion in glioblastoma cells, but not in astrocytes. Forced expression of c-Met or Notch-1/Notch-2 transcripts lacking the 3′-UTR sequences partially reversed the effects of miR-34a on cell cycle arrest and cell death in glioblastoma cells and stem cells, respectively. Also, in vivo transient expression of miR-34a in glioblastoma cells strongly inhibited intracranial xenograft growth. We therefore showed that miR-34a suppresses brain tumor growth by targeting c-Met and Notch. We subsequently investigated the effect of miR-34a on glioblastoma stem cell malignancy and differentiation. We transfected 0308 and 1228 glioblastoma stem cells with 30 nM pre-miR-34a or control miR for 72 hours and assessed the cells for cell cycle status, cell proliferation, cell migration and apoptosis by propidium iodide flow cytometry, cell counting, scratch migration assay and annexin V flow cytometry, respectively. We also assessed the effect of miR-34a on stem cell differentiation into neurons, astrocytes or oligodendrocytes, by immunohistochemistry staining for CD133, nestin and differentiation markers including Claudin, GFAP, and Tuj-1. miR-34a slightly inhibited cell proliferation in both stem cell lines. miR-34a also induced G1/S cell cycle arrest. Moreover, miR-34a restoration led to a slight increase in stem cell death in both stem cell lines and also strongly inhibited migration in 1228 stem cells. Importantly, miR-34a treatment of stem cells reduced CD133 staining and increased differentiation marker staining. These data suggest a role for miR-34a in the regulation for glioblastoma stem cell malignancy and differentiation. Supported by a University of Virginia Cancer Center Pilot Project Grant.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2067.
Abstract 2072: Systematic functional analysis of microRNAs by transfection of 1129 miRNAs into prostate cancer cells
Authors: Ostling Paivi , Leivonen Suvi-Katri , Aakula Anna , Kohonen Pekka , Makela Rami , Perala Merja , Kallioniemi Olli 
Published: February 2011

Abstract
The molecular mechanisms behind prostate cancer development, progression and therapy failure are incompletely understood, but the androgen receptor (AR) is almost invariably involved. Altered microRNA (miRNA) expression profiles have recently been demonstrated in a large number of cancer types, including prostate cancer. These short RNA molecules of ∼21 bases regulate mRNA stability and translation by base-pairing mainly to the 3’-untranslated region (3′UTR) of their targets.
In this study, we analyzed the functional impact of miRNA transfections on prostate cancer cell growth, survival, and expression of the AR protein. Seven prostate cell lines (LNCaP, LAPC-4, MDA-PCa-2b, 22Rv1, CWR-1R, RWPE-1, and EP156T) were screened with 1129 miRNA mimics (Ambion, Dharmacon). Cell viability was measured with CellTiter-Glo® (CTG, Promega) whereas AR, cell proliferation (Ki67) and apoptosis (cPARP) were detected with specific antibodies using protein lysate microarrays as described in our recent publication on estrogen receptor targeting miRNAs (Leivonen et al., Oncogene 2009). Seventy-one of the miRNAs had anti-proliferative or pro-apoptotic functions when transfected to the prostate cancer cell lines. In addition, 17 of these miRNAs down-regulated the AR protein. Western blots were used to verify knockdown, and the direct functional role of the miRNAs was clarified by 3′UTR assays and by analyses of down-stream consequences of the knockdowns.
In summary, we have systematically defined those miRNAs that are critical for prostate cancer growth, survival and the expression of the androgen receptor. This integrated, multi-parametric profiling provides new evidence of the role of miRNAs in prostate cancer as well as novel clues for therapeutic targeting by manipulating key pathways and cell survival mechanisms by miRNA transfections.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2072.
Abstract 2077: MicroRNA signature of hyperplastic enlarged lobular units (HELU) from patients with high risk of breast cancer
Authors: Nilsson Sofie , Landberg Göran 
Published: February 2011

Abstract
In order to detect early pathological changes in breast tissue, which could reveal the underlying mechanism to cancer progression, we investigated the microRNA (miRNA) expression profile in hyperplastic enlarged lobular units (HELUs). HELUs arise from normal terminal duct lobular units (TDLUs) and are potentially the earliest histologically identifiable alterations in the development of breast cancer.
TDLUs and HELUs, from formalin-fixed paraffin embedded tissue from patients with high risk of developing breast cancer, were laser capture microdissected and the RNA was extracted. Expression profiles were obtained using a qRT-PCR-based array analyzing 667 human miRNAs.
In the first set of miRNA array analyses of paired samples from four specimens with early HELUs, we obtained a list of 16 downregulated and 10 upregulated miRNAs with a significant change (p&lt;0.05) in expression. Among the most pronounced altered miRNAs were miR-136, miR-301b, miR-302b and miR-576-5p.
To validate these results, more paired samples of fully developed HELUs will be added to the study and candidate miRNAs will be further validated using qPCR and in situ hybridization of formalin fixed specimens using a selection material of 100 patients with high risk of breast cancer. These ongoing miRNA analyses will potentially reveal additional miRNAs that are linked to the development of TDLUs towards HELUs as well as substantiating the frequency of the various alterations observed.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2077.
Abstract 2084: Tumor suppressor microRNA miR-34 inhibits human pancreatic cancer stem cells
Authors: Tang Wenhua , Ji Qing , Hao Xinbao , Li Ling , Jeffrey DeSano , Fearon Eric R. , Lawrence Theodore S. , Xu Liang 
Published: February 2011

Abstract
MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. We show that miR-34 directly regulates Notch and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells.
We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines and the potential link to cancer stem cells. Restoration of miR-34 expression in the cancer cells by miR-34 mimics or lentiviral miR-34 downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cancer cells to chemotherapy and radiation. We identified that CD44+/CD133+ cancer cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor-initiation in vivo. Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer. Our data support that miR-34 may be involved in cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in cancer stem cell self-renewal and/or cell fate determination. Currently, we are exploring the nanoparticle-targeted delivery of miR-34 to cancer stem cells as a novel molecular therapy for human pancreatic cancer, based on our patented nanobiotechnology which has been approved by FDA for clinical trials. Taken together, our results demonstrate that restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic/gastric cancer with loss of p53-miR34, potentially via inhibiting cancer stem cells. The project is funded by NIH grants CA121830, CA128220 and CA134655 (to L. Xu.).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2084.
Abstract 209: Gamma linolenic acid sensitizes pancreatic cancer cells to chemotherapy
Authors: Espinoza Ingrid C. , Busby Robert , Lupu Ruth 
Published: February 2011

Abstract
In pancreatic cancer both chemotherapy and radiotherapy have shown deficient results in treating the disease, indicating a fundamental need for more efficient therapies. Most pancreatic cancer patients present with an advanced form of the disease that is incurable by surgery, and will receive palliative treatment in the form of surgery, chemotherapy, radiotherapy and symptom control. There are few standard chemotherapeutics for the treatment of pancreatic cancer, although Gemcitabine and 5-Fluorouracil (5-FU) are the most widely used. In search for specific nutritional, and/or pharmacological agents to target pancreatic cancer cells/tissues we identified a series of nutritional supplements known as polyunsaturated fatty acids (PUFAs) that have an inhibitory effect on cancer cells. However, Gamma-Linolenic-Acid (GLA), a member of the ω-6 family of PUFAs exerts selective cytotoxic effects on pancreatic cancer cells without affecting normal epithelial cells. The goal of our study was to determine whether GLA could sensitize the targeted pancreatic cancer cells to chemotherapeutic agents (Gemcitabine or 5-FU). Therefore, pancreatic cancer cells were treated initially with GLA followed by each of the chemotherapeutic agents separately: Our results demonstrated that: 1) GLA induced growth inhibition and apoptosis of pancreatic cancer cells (Panc-1 and BxPC3); 2) the combination of GLA and Gemcitabine or GLA and 5-FU: a) promote a synergistic inhibitory effect on the growth of pancreatic cancer cells; b) inhibition of anchorage-independent growth; and 4) inhibition of morphogenesis in 3-D matrigel culture. These results show that GLA increases the sensitivity of pancreatic cancer cells to chemotherapy through a synergistic effect with Gemcitabine or 5-FU, implying that GLA could be used as a supportive drug for the pancreatic cancer patients receiving the current chemotherapeutic regimens.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 209.
Abstract 2099: Induction of tumor suppressor genes IL24 and IL32 by microRNA-205 in prostate cancer
Authors: Majid Shahana , Dar Altaf A. , Saini Sharanjot , Chen Yi , Shahryari Varahram , Liu Jan , Zaman Saif , Hirata Hiroshi , Yamamura Soichiro , Ueno Koji , Tanaka Yuichiro , Khatri Gaurav , Carroll Peter R. , Dahiya Rajvir 
Published: February 2011

Abstract
Introduction and Objective: MicroRNAs are small noncoding RNAs that regulate the expression of approximately 30% of all human genes, either inhibiting target mRNA translation or inducing its degradation. These genes are abnormally expressed in human malignancies, making their biological importance increasingly apparent. Given the functional complexity of miRNA mediated gene regulation, it is unlikely that miRNAs are limited to gene silencing. The main objective of this study was to investigate the involvement of miRNA-205 in prostate carcinogenesis and whether miR-205 functions as a tumor suppressor by transcriptionally up-regulating tumor suppressor genes IL24 and IL32.
Methods: The methods employed in this study include quantitative-real time PCR; western blot; in-situ hybridization; fluorescence-activated cell sorting assays for cell cycle distribution and apoptosis; assays for cell viabiltity, clonability, migration and invasiveness of prostate cancer cells. Luciferase reporter and mutational assays; nuclear run-on, in-vitro transcription and chromatin immunoprecipitation assays were also performed.
Results: Our results indicated that miR-205 expression levels are either silenced or significantly lower in prostate cancer cell lines and prostate tumors when compared to non-malignant prostate cell lines or benign prostate hyperplasia tissues respectively. By scanning gene promoters for sequences complementary to miR-205, we identified putative miR-205 target sites in the promoters of IL24 and IL32 tumor suppressor genes. Over-expression of miR-205 in prostate cancer cells (PC-3) induced the expression of both genes by targeting specific sites in their promoters. Transfection of miR-205 impaired cancer cell growth, clonability, migration, invasiveness and induced apoptosis and cell cycle arrest by interfering with the expression of genes involved in these pathways. MicroRNA-205 induced in-vitro transcription and caused enrichment of histone markers indicative of transcriptionally active promoters in IL24 and IL32 genes. Luciferase reporter and mutational assays indicated that IL24 and IL32 are the direct targets of miR-205.
Conclusion: For the first time we have shown that microRNA-205 specifically activates tumor suppressor genes IL24 and IL32 by targeting complimentary binding sites in their promoters, corroborating a new function for miRNAs in regulating gene transcription. Such a function of microRNAs may contribute to the novel therapeutic approach in the treatment of prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2099.
Abstract 2102: Exogenous microRNA-101 suppresses cell proliferation by downregulation of cyclooxygenase-2 expression in prostate cancer cell line
Authors: Hao Yubin , Pang Xiaowu , Zhao Yuan , Califano Joseph A. , Gu Xinbin 
Published: February 2011

Abstract
MicroRNAs, ∼22 nt non-coding small RNAs, have been newly focused as a potential cancer diagnostic biomarker and therapy target, because aberrant expressions of miRNAs have been often found to involve in tumorigenesis, cancer development and progression. For instance, microRNA-101 (miR-101) is significantly down-regulated in several types of cancer. In this study, we investigated the function of miR-101 on regulation of gene expression in cancer cells. A stable miR-101 over-expressed prostate cancer cell line (BPH1CAFTDmiR101) was established by using lentivirus-delivery system. Over-expressed miR-101 level in the stable transfected cell can be detected after the 5th or 100th cell culture passages and approximately 10-fold higher than non-transfected BPH1CAFTD cells. We found that over-expressed miR-101 suppressed cyclooxygenase-2 (COX-2) protein expression in BPH1CAFTDmiR101 cells. The miR-101 targeted gene was determined by using luciferase reporter gene, which carry 3’-UTR (NM_000963 3’-UTR 1735-1741) of COX-2 mRNA. The results indicated that miR-101 directly targets COX-2 gene and down-regulates COX-2 protein expression by binding to 3’-UTR of COX-2 mRNA. Interestedly, the reduced COX-2 protein expression in BPH1CAFTDmiR101can be restored by transient transfection of COX-2 3′UTR fragment. Compared with BPH1CAFTD cells, BPH1CAFTDmiR101 proliferation and colony formation were significantly inhibited, and the expressions of a series of cell proliferation-related protein were significantly changed, such as the levels of EGFR, PCNA, and Bcl-2 were decreased and the level of p53 was increased. In addition, MMP-15 protein level, a metastasis related protein, was also noticeably reduced. Taking together, our finings demonstrate that miR-101 inhibits prostate cancer cell proliferation by directly targeting COX-2 to down-regulating its protein level. The miR-101 may function as tumor suppressor and a potential target for cancer diagnosis and therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2102.
Abstract 2103: miR-140 and miR-192 are potential tumor suppressors through inhibiting cellular proliferation and restoring cell cycle control in breast cancer cell lines
Authors: Song Bo , Karaayvaz Mihriban , Ju Jingfang 
Published: February 2011

Abstract
Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNAs in regulating expressions of multiple mRNA targets mostly by binding at the 3’-UTRs to inhibit mRNA translation or facilitate mRNA cleavage. MiRNAs are involved in the control of many fundamental cellular and physiological processes and mounting evidence indicates that miRNAs play important roles in human cancers acting either as oncogenes or tumor suppressor genes through their global impact on multiple genes and pathways. Previous studies from our group have discovered two important miRNAs, miR-140 and miR-192, in suppression of cellular proliferation and triggering cell cycle arrest in both colon cancer and osteosarcoma cell lines. In this study, we further elucidate the molecular and cellular impact of these two miRNAs in breast cancer. miR-140 or miR-192 were over-expressed by transient transfection in a panel of breast cancer cell lines such as MCF-7 and MDA-MB-231. The proliferation of MCF-7 cells transfected with miR-140 or miR-192 was dramatically decreased at 100 nM while the control miRNA has no effect. Inhibition of proliferation by miR-140 or miR-192 was also observed in MDA-MB-231 cells but less potent than MCF-7 cells at the equal concentration. MCF-7 cells transfected with miR-140 or miR-192 were arrested at G2/M phase of the cell cycle. The cell cycle check point control genes p53 and p21 were induced by over-expressing miR-140 or miR-192. The endogenous miR-140 or miR-192 expression was induced in MCF-7 cells treated with methotraxate (MTX) accompanied with increased expression of p53. Blocking endogenous miR-140 or miR-192 by locked nucleic acid (LNA) modified anti-miRNA increased cellular proliferation rate in MCF-7 cells. In conclusion, miR-140 and miR-192 may have therapeutic potential in breast cancer.
Keywords: microRNA, breast cancer, miR-140, miR-192
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2103.