scholarly journals The guardians of the genome dependent tumor suppressor miRNAs network

2009 ◽  
Author(s):  
Lakshmanane Boominathan ◽  
Lakshmanane Boominathan
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Mirnas

Bifidobacterium longumSuppresses Murine Colorectal Cancer through the Modulation of oncomiRs and Tumor Suppressor miRNAs

2019 ◽  
Vol 71 (4) ◽  
pp. 688-700 ◽  
Author(s):  
Cinderella A. Fahmy ◽  
Amira M. Gamal-Eldeen ◽  
Enas A. El-Hussieny ◽  
Bassem M. Raafat ◽  
Nayra S. Mehanna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Mirnas

Abstract 2107: Deregulation of tumor suppressor miRNAs results in Six1 oncogene overexpression in pediatric and adult human cancers

2010 ◽  
Author(s):  
J. Saadi Imam ◽  
Kalyan Buddavarapu ◽  
Jennifer S. Lee-Chang ◽  
Peter Hornsby ◽  
Yidong Chen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Adult Human ◽  
Human Cancers ◽  
Tumor Suppressor Mirnas

Comparison of miRNA Expression Profiles in Leukemia-Derived Microvesicles and Corresponding Leukemia Cells and Analysis of Their Roles in Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1388-1388
Author(s):  
Xiaomei Chen ◽  
Fang Liu ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Mirna Expression ◽  
Tumor Suppressors ◽  
Target Genes ◽  
Expression Profiles ◽  
K562 Cells ◽  
Cell Types ◽  
Leukemic Cells ◽  
Mirna Expression Profiles ◽  
Tumor Suppressor Mirnas

Abstract Abstract 1388 Microvesicles(MVs) are small exosomes of endocytic origin released by normal healthy or damaged cell types, including leukemic cells. MVs have been considered as cell dust, however, recent data bring evidences that MVs generated during cell activation or apoptosis can transfer biologic messages between different cell types. MicroRNAs (miRNAs) have been demonstrated to be aberrantly expressed in leukemia and the overall miRNA expression could differentiate normal versus leukemia. The MVs expressing miRNAs were found in the primary tumors. However it is currently unknown whether miRNA content changes in MVs derived from leukemic cells. Here we compared the miRNA expression in leukemia-derived MVs to corresponding leukemia cells and analysed their roles in leukemia. K562 cells were cultured and collected. MVs derived from K562 cells were also isolated. The presence and levels of specific miRNAs from both MVs derived from K562 cells and K562 cells were determined by Agilent miRNA microarray analysis probing for 888 miRNAs. Some selected miRNAs were verified by real time qRT-PCR. Bioinformatic software tools were used to predict the target genes of identified miRNAs and define their function. Our results showed that 77 and 122 miRNAs were only expressed in MVs and K562 cells, respectively. There were significant differences in miRNA expression profiles between MVs and K562 cells. We also found that 112 miRNAs were co-expressed in MVs and K562 cells. This observaton may suggest that compartmentalization of miRNAs from cells into to MVs, for at least some miRNAs, is an active (selective) process. Among those abnormally expressed miRNAs, some have been proposed oncomiRNAs or tumor suppressors. For example, miR-155, has been proposed as oncomiRNA, was abnormally expressed only in MVs in our study, suggesting that oncomiRNA was present in MVs. Further analysis revealed that 39 potential target genes regulated by miR-155. Among them, 4 genes involed in oncogenes and the signal genes. OncomiRNAs such as miR-27a and miR-21 expressed in both MVs and corresponding cells, indicating that MVs bear miRNA characteristic of the cell origin. MVs, released into the leukemia microenvironment, play an important role in leukemia. In contrast to oncomiRNAs, if miRNA is associated with tumor suppressive activity, it is regarded as a tumor suppressor (oncosuppressor). The aberrantly expressed miR-125a-3p, miR-125-5p,miR-27b, which have implicated as tumor suppressors, appear in both cellular and MVs of leukemia in our study. MiR-125a-3p, miR-125-5p and miR-27b regulated 308 potential target genes. To our knowledge, 10 of them are tumor suppression genes. It is possible that these aberrantly expressed tumor suppressor miRNAs decreased or lost their roles of tumor suppression, which led to decrease or loss their roles of regulating their target genes including oncogenes, consequently resulted in leukemia. Since K562 cells presented t(9;22), we further examined the predicted function of the 6 expressed miRNAs located in chrosome 9 (hsa-miR-188-5p,hsa-miR-602)and 22(hsa-let-7b,hsa-miR-1249,hsa-miR-130b,hsa-miR-185), which expressed both in the MVs and K562 cells. Using the TargetScan, we found 442 predicted targets regulated by 6 miRNAs. Those miRNAs may play roles in leukemia via these 422 genes. This study is the first to identify and define miRNA expression between K562 cells presented t(9;22), derived from K562 cells and their corresponding cells. We found significant differences in miRNA expression between MVs and corresponding leukemia. K562 cells released MVs riched in miRNAs including oncomiRNAs or tumor suppressor miRNAs into leukemia microenvironment, which play a role in leukemia via regulating their targer genes including oncogenes, consequently resulted in leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Mir-193 Family Antagonizes Stem Cell Pathways and Is a Potent Tumor Suppressor in Childhood and Adult Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1244-1244
Author(s):  
Kathrin Krowiorz ◽  
Razan Jammal ◽  
Stephan Emmrich ◽  
Arefeh Rouhi ◽  
Michael Heuser ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Family Members ◽  
S Phase ◽  
The Impact ◽  
Tumor Suppressor Mirnas ◽  
Acute Myeloid

Abstract MicroRNAs (miRNAs) are essential for maintenance and differentiation of normal hematopoietic cells and their dysregulation is strongly implicated in leukemias. In order to identify tumor suppressor miRNAs in the context of hematological malignancies, we performed two complementary miRNA expression screenings in normal hematopoiesis as well as in childhood and adult acute myeloid leukemias (AML). We reasoned that tumor suppressor miRNAs are upregulated in mature myeloid cells, as compared to normal hematopoietic stem and progenitor cells (HSPCs), and downregulated in AML. Based on this screening strategy, we identified the miR-193 family members as potent suppressors of HSPC activity and AML growth. During normal hematopoiesis mmu-miR-193a-3p is exclusively expressed in mature myeloid cells and absent in normal HSPCs. Accordingly, in a cohort of 165 pediatric AML patients hsa-miR-193b-3p was broadly repressed throughout the cytogenetically characterized subgroups. In addition, in a cohort of 43 adult AML patients, its homolog hsa-miR-193a-3p was significantly upregulated in APL cases (p=0.0025, n=7) compared to bone marrow from healthy donors (n=5). To assess the impact of the miR-193 family members on AML maintenance and development, we lentivirally expressed miR-193a/b in the MLL-rearranged cell lines ML2 and THP1, which induced monocytic differentiation in concert with calcitriol treatment, measured by CD11b/CD14 expression (p=0.024). Consistently, enforced miR-193-expression led to a significant growth disadvantage in ML2 and THP1 cells (p=<0.001 and p=0.02, respectively) as well as to reduced colony formation (p=0.008) in methylcellulose-based colony-forming unit (CFU) assays. Noteworthy, these effects were not restricted to MLL-rearranged AML cell lines only, but were also evident in six other AML cell lines representing the most common AML subgroups, such as t(8;21) and t(15;17). Beyond the growth-suppressive and differentiation-inductive effect of miR-193 in human AML cell lines, overexpression of miR-193a caused a significant decrease of proliferation in murine bone marrow cells immortalized in vitro by retroviral expression of Hoxa9 or Hoxa9 and Meis1 (p=0.019 and p=0.008, respectively). Based on these findings in AML, we further investigated the impact of the miR-193 family on normal hematopoiesis. We retrovirally expressed miR-193a in 32D cells treated with granulocyte-colony stimulating factor (G-CSF), which resulted in a strong induction of myeloid differentiation already after day 2 (p=0.006) as assessed by CD11b/Gr-1 surface marker expression. We lentivirally transduced mouse lineage negative (Lin-) HSPCs and transplanted them into irradiated isogenic recipients. Bleedings performed on weeks 4, 8 and 11, as well as the examination of the bone marrow on week 11, showed a severe competitive disadvantage of miR-193-transduced cells (week 11: 2% GFP+ miR-193- vs. 25% GFP+ miR-NSC-transduced cells). These results were further refined using highly purified ESLAM (CD45+ EPCR+ CD48− CD150+) HSCs which failed to reconstitute hematopoiesis when overexpressing miR-193a, indicated by the absence of miR-193a/GFP+ cells at week 8 post transplantation. These observations might be explained by a potent G1 cell cycle arrest in HSPCs when overexpressing miR-193a/b (4-fold decrease in the S phase population) and induction of apoptosis. Our results in normal and malignant hematopoiesis suggested that the miR-193 family acts globally through targeting relevant stem cell pathways. To validate this hypothesis we quantified the knockdown of ten predicted miR-193 target genes. qRT-PCR analysis confirmed the down regulation of KIT, KRAS, SOS2 (key components of the MAPK signaling pathway) and CCND1, a CDK regulator of G1/S phase transition. We propose a dual regulatory platform where firstly, miR-193 targets CCND1 and controls the cell cycle kinetics of stem cells. Secondly, miR-193 interferes with the KIT proto-oncogene and the RAS pathway thereby inhibiting crucial pro-proliferation and anti-apoptotic signaling cascades. Taken together, we identified the miR-193 family as a pan-tumor suppressor in childhood and adult AML. Its anti-leukemic effect is mediated by targeting the stem cell KIT/SOS2/RAS/RAF axis. Disclosures No relevant conflicts of interest to declare.

The Promise of miRNA Replacement Therapy for Hepatocellular Carcinoma

2019 ◽  
Vol 19 (5) ◽  
pp. 290-304 ◽  
Author(s):  
Mahmoud Elhefnawi ◽  
Zeinab Salah ◽  
Bangly Soliman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Mortality Rate ◽  
Tumor Suppressor ◽  
Noncoding Rnas ◽  
Efficient Delivery ◽  
Post Transcriptional Regulation ◽  
Tumor Suppressor Mirnas

Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globally, and about 780,000 new cases each year. Tumor suppressor miRNAs represent a class of noncoding RNAs, which exhibit decreased or inhibited expression in the case of carcinogenesis. Therefore, the replacement of these molecules leads to post-transcriptional regulation of tens to hundreds of oncogenic targets and limiting the tumor. Interestingly, there is a group of tumor silencer miRNAs that have been highlighted in HCC and herein, our review will discuss the prominent examples of these miRs in terms of their efficient delivery using vectors, nano-delivery systems, their successful models either in vitro or in vivo and pre-clinical trials. Collectively, tumor suppressor miRNAs can act as novel therapeutics for HCC and more studies should be directed towards these promising therapeutics.

DLK1-DIO3 Region as a Source of Candidate Tumor Suppressor miRNAs in Papil- Lary Thyroid Carcinoma

2020 ◽  
Author(s):  
Leonardo Augusto Marson ◽  
Letícia Ferreira Alves ◽  
Micheli Severo Sielski ◽  
Cristina Pontes Vicente ◽  
Edna Teruko Kimura ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Genomic Region ◽  
And Migration ◽  
The Individual ◽  
Computational Resources ◽  
The Impact ◽  
Tumor Suppressor Mirnas ◽  
Shed Light

Abstract Background: DLK1-DIO3 genomic region comprises one of the largest microRNA (miRNAs) clusters in human genome. In previous studies we showed the downregulation of several miRNAs from the genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region the individual contribution of these molecules to PTC development and progression remains unclear. Methods: We used different computational resources to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. Results: Our analysis suggests that 12 miRNAs from this region cooperate to modulate distinct cancer-relevant biological processes, potentially responding for most of the impact of DLK1-DIO3-derived miRNAs to PTC development and progression. The overexpression of miR-485-5p in two PTC cell lines decreased proliferation and migration, confirming the biological relevance of in silico data. Conclusion: Our results shed light on the role of DLK1-DIO3 region, harboring several tumor suppressor miRNAs in thyroid cancer and open perspectives for the functional exploration of these miRNAs as therapeutic targets for PTC.

Ascites in ovarian cancer: MicroRNA deregulations and their potential roles in ovarian carcinogenesis

2021 ◽  
pp. 1-16
Author(s):  
Luděk Záveský ◽  
Eva Jandáková ◽  
Vít Weinberger ◽  
Veronika Hanzíková ◽  
Ondřej Slanař ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Tumor Suppressors ◽  
Chemotherapy Resistance ◽  
Gynecologic Malignancy ◽  
Clinical Investigations ◽  
Ovarian Carcinogenesis ◽  
Tumor Suppressor Mirnas

Ovarian cancer comprises the most lethal gynecologic malignancy and is accompanied by the high potential for the incidence of metastasis, recurrence and chemotherapy resistance, often associated with a formation of ascitic fluid. The differentially expressed ascites-derived microRNAs may be linked to ovarian carcinogenesis. The article focuses on a number of miRNAs that share a common expression pattern as determined by independent studies using ascites samples and with regard to their functions and outcomes in experimental and clinical investigations. Let-7b and miR-143 have featured as tumor suppressors in ovarian cancer, which is in line with data on other types of cancer. Although two miRNAs, i.e. miR-26a-5p and miR-145-5p, act principally as tumor suppressor miRNAs, they occasionally exhibit oncogenic roles. The performance of miR-95-3p, upregulated in ascites, is open to debate given the current lack of supportive data on ovarian cancer; however, data on other cancers indicates its probable oncogenic role. Different findings have been reported for miR-182-5p and miR-200c-3p; in addition to their presumed oncogenic roles, contrasting findings have indicated their ambivalent functions. Further research is required for the identification and evaluation of the potential of specific miRNAs in the diagnosis, prediction, treatment and outcomes of ovarian cancer patients.

Abstract LB-169: Ovarian cancer cells selectively release exosomes containing tumor suppressor miRNAs to maintain SRC-mediated oncogenic activities

2016 ◽  
Author(s):  
Mohammed H. Rashed ◽  
Pinar Kanlikilicer ◽  
Cristian Rodriguez Aguayo ◽  
Nashwa N. Kabil ◽  
Martin Pichler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Tumor Suppressor Mirnas
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