Differentiating soft tissue leiomyosarcoma and undifferentiated pleomorphic sarcoma: A miRNA analysis

Guled, Mohamed; Pazzaglia, Laura; Borze, Ioana; Mosakhani, Neda; Novello, Chiara; Benassi, Maria Serena; Knuutila, Sakari

doi:10.1002/gcc.22179

Cited by 39 publications

(47 citation statements)

References 33 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…analysis, no effect of miR-199a-5p expression on patients' survival was detected, however, non-parametric correlation analyses demonstrated a correlation with tumor entity (P=0.014, Kruskal-Wallis test). This is concordant with the results of a previous study by Guled et al (28), describing a diagnostic role of miR-199-5p for the identification of undifferentiated pleomorphic sarcoma compared to leiomyosarcoma. It has also been demonstrated that low miR-199a-5p expression is associated with a poorer outcome in serous ovarian carcinoma (29), non-small cell lung carcinoma measured in patients' sera (30) and renal cell carcinoma (31).…”

Section: Discussionsupporting

confidence: 92%

miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

et al. 2016

View full text Add to dashboard Cite

Abstract. Soft tissue sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin. Partly due to hypoxia, an aggressive and radioresistant phenotype frequently develops, resulting in poorer patient outcome. microRNAs (miRNAs) are tiny, non-coding regulators of gene expression and in situations of cellular stress situations may predict clinical progression and patient outcome. In the present study, hypoxia-associated miR-199a-5p expression in 96 soft tissue sarcoma samples was analysed by reverse transcription-quantitative polymerase chain reaction and associations between miR-199a-5p expression and patient clinicopathological characteristics and survival were measured. Additionally, luciferase reporter assays analyzed the post-transcriptional regulation of hypoxia-associated genes hypoxia-inducible factor 1α (HIF-1α), oxidative stress induced growth inhibitor 2 (OSGIN2) and vascular endothelial growth factor (VEGF) by miR-199a-5p. Survival analyses indicated that low expression of miR-199a-5p was significantly correlated with poorer tumor-specific survival (univariate Cox's-Regression analyses; relative risk=1.92, P=0.029). Furthermore, it was demonstrated that the 3'UTR of HIF-1α and OSGIN2 genes were regulated by miR-199a-5p in-vitro, although the 3'UTR of VEGF was not. To the best of our knowledge, this is the first report demonstrating the regulation of the 3'untranslated region of the OSGIN2 gene by miR-199a-5p and a significant correlation between low miR-199a-5p expression and a poor outcome of patients with soft tissue sarcoma. IntroductionMicroRNAs (miRNAs) are small (18-25 nt), non-coding RNAs of endogenous origin. To date, >2,500 different mature miRNA species have been detected in humans (1). Following maturation, double-stranded miRNAs are immediately bound to Argonaute proteins and unwound. In the single-stranded conformation, they build up the active component of the RNA-induced silencing complex (RISC) (2,3). miRNAs bind to complementary sequences in the 3'untranslated region (UTR) of their target mRNAs, thus acting as translational repressors. This action is primarily performed by a hexamer sequence at the 5'UTRs called the seed sequence and the subsequent translocation to the P-bodies (processing bodies), which are specialized cellular components for RNA silencing and decay (4,5). Due to the simple target recognition sequence and the vast number of different species of miRNA, it is estimated that ~60% of the human protein-coding genes are regulated post-transcriptionally by miRNAs (6). Due to their high abundance and immense impact on cellular gene expression profiles, miRNAs serve an important role in cellular proliferation and differentiation processes. Furthermore, they contribute to the adaptation to cellular stress, including stress caused by an acidic or hypoxic environment (7,8).Hypoxia, the state of decreased oxygen saturation in a tissue, is a major problem in the treatment of solid tumors. Due to rapid growth, regions in solid tumors tend to be cut off from oxygen ...

show abstract

Section: Discussionsupporting

confidence: 92%

miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Expression of polo-like kinase 2 (PLK2) and miRs -100, -574, -22, -21 and -30 were negatively correlated with talazoparib sensitivity (Figure 6). MiR-22 is repressed in Ewing sarcoma expressing EWS-FLI1, and was low in leiomyosarcoma and miR-22 expression was negatively correlated with sensitivity to talazoparib (58). In addition, cMyc expression can produce a down regulation of miR-22 (59).…”

Section: Discussionmentioning

confidence: 99%

Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression

Teicher

Polley

Kunkel

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The diversity in sarcoma phenotype and genotype make treatment of this family of diseases exceptionally challenging. Sixty-three human adult and pediatric sarcoma lines were screened with 100 FDA approved oncology agents and 345 investigational agents. The investigational agents library enabled comparison of several compounds targeting the same molecular entity allowing comparison of target specificity and heterogeneity of cell line response. Gene expression was derived from exon array data and microRNA expression was derived from direct digital detection assays. The compounds were screened against each cell line at 9 concentrations in triplicate with an exposure time of 96 hrs using Alamar blue as the endpoint. Results are presented for inhibitors of the following targets: aurora kinase, IGF-1R, MEK, BET bromodomain, and PARP1. Chemical structures, IC50 heat maps, concentration response curves, gene expression and miR expression heat maps are presented for selected examples. In addition, two cases of exceptional responders are presented. The drug and compound response, gene expression and microRNA expression data are publicly available at http://sarcoma.cancer.gov. These data provide a unique resource to the cancer research community.

show abstract

“…As regulators of gene expression, miRNAs are involved in regulating multiple biological processes, including cell growth, apoptosis, tissue growth, tissue morphogenesis and the regulation of tumor growth (17)(18)(19). Highly expressed in human endothelial cells, miR-126 is closely associated with several types of cancer and is possibly one of the future means for cancer treatment (4,20).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-126 enhances the sensitivity of osteosarcoma cells to cisplatin and methotrexate

Jiang

Cheng

2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. The establishment of novel chemotherapy drugs for osteosarcoma is urgently required, and the mechanisms and effects of cisplatin (DDP) and methotrexate (MTX) in the current treatment of osteosarcoma have not been fully elucidated. The present study aimed to observe the effect of DDP, MTX and rapamycin on osteosarcoma cell proliferation and apoptosis, and to investigate the association between miR-126 and the effects of DDP and MTX in osteosarcoma cells. miR-126-overexpressing and -silencing lentiviral vectors were constructed, and MG63 and U-2 OS osteosarcoma cells were infected. An MTT assay was conducted to detect transfected cell proliferation, and the effects of the chemotherapy drugs on transfected cell apoptosis were detected by flow cytometry. The cell cycle of the transfected cells was analyzed via flow cytometry. As the miR-126-overexpressing and -silencing osteosarcoma cell lines were successfully constructed, it was observed that DDP and MTX inhibited osteosarcoma cell proliferation. With the decreased expression of miR-126, the sensitivity of osteosarcoma cells to DDP and MTX was reduced at the same concentration. The flow cytometry suggested that DDP and MTX could promote the apoptosis of osteosarcoma cells with overexpressed miR-126, whereas they could not significantly impact the apoptosis of the miR-126-silenced osteosarcoma cells. Meanwhile, DDP inhibited the cell cycle of the miR-126-overexpressing osteosarcoma cells. In conclusion, DDP and MTX inhibited the proliferation and promoted the apoptosis of the osteosarcoma cells, and these processes were dependent upon the expression of miR-126.

show abstract

Differentiating soft tissue leiomyosarcoma and undifferentiated pleomorphic sarcoma: A miRNA analysis

Cited by 39 publications

References 33 publications

miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression

MicroRNA-126 enhances the sensitivity of osteosarcoma cells to cisplatin and methotrexate

Contact Info

Product

Resources

About