&lt;p&gt;Long Non-Coding RNA GAS5 Targeting microRNA-21 to Suppress the Invasion and Epithelial–Mesenchymal Transition of Uveal Melanoma&lt;/p&gt;

Ying, Qi; Cui, Qingqing; Zhang, Wenjing; Yao, Renjie; Xu, Dong; Zhang, Fengyan

doi:10.2147/cmar.s260866

Cited by 16 publications

(8 citation statements)

References 24 publications

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“…As a competing endogenous RNA for miR-96-5p, lncRNA GAS5 promotes renal tubular epithelial brosis (34). Likewise, LncRNA GAS5 directly bind to miR-21 to suppress EMT in human uveal melanoma (35). By coincidence, our previous research con rmed that lncRNA GAS5 can competitively combine with miR-21 to regulate PTEN and in uences EMT in HPMCs(36).…”

Section: Discussionmentioning

confidence: 93%

Mechanisms of human umbilical cord mesenchymal stem cells-derived exosomal lncRNA GAS5 in alleviating EMT of HPMCs via Wnt/β-catenin signaling pathway

Huang

Fan

Yang

2023

Preprint

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The aim of this study was to reveal mechanisms of exosomal lncRNA GAS5 derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) on epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) under high glucose (HG) conditions. HPMCs were stimulated with 2.5% glucose. The effects on EMT of HPMCs were observed by using an hUC-MSC conditioned medium (hUC-MSC-CM) and extracted exosomes. Four groups were established: ① control group,②HG group (2.5% glucose), ③conditioned medium (CM) group (2.5% glucose and 7.5% MSC-CM), and ④ exosome group (2.5% glucose and exosomes extracted from 7.5% MSC-CM), all treated for 48 h. After hUC-MSCs were transfected with GAS5 siRNA, exosomes were extracted to act on HPMCs. Western blot assay and real-time PCR were used to detect expressions of EMT markers, PTEN and Wnt/β-catenin pathway in HPMCs. Based on the real-time PCR, the changes in levels of expression of lncRNA GAS5 and miR-21 were detected. We found that HG could induce the EMT of HPMCs. Compared with the HG group, the hUC-MSC-CM could alleviate EMT of HPMCs induced by HG through exosomes. Exosomes in the hUC-MSC-CM entered HPMCs, by transferring lncRNA GAS5 to HPMCs, which down-regulates miR-21 and up-regulates PTEN, thus finally alleviating EMT of HPMCs. Wnt/β-catenin pathway plays an essential role in alleviating EMT of HPMCs by exosomes in the hUC-MSC-CM. By transferring lncRNA GAS5 to HPMCs, exosomes derived from hUC-MSCs may competitively bind to miR-21 to regulate suppression on target PTEN genes and alleviate EMT of HPMCs through Wnt/β-catenin pathway.

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Section: Discussionmentioning

confidence: 93%

Mechanisms of human umbilical cord mesenchymal stem cells-derived exosomal lncRNA GAS5 in alleviating EMT of HPMCs via Wnt/β-catenin signaling pathway

Huang

Fan

Yang

2023

Preprint

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“…Genetic disruption via miR-NAs on the oncogenes or tumour suppressor genes may impact on malignant phenotypes of UM. Literature has shown that the pharmacological effects of miRNAs on UM are likely to be mediated through influencing cell proliferation and invasion [172,173]. Thus, miRNAs may be applicable in the diagnosis and prognosis of UM as well as with potential values in treating UM.…”

Section: Genetic Disruption Via Micrornas (Mirnas) In Ummentioning

confidence: 99%

Development of new therapeutic options for the treatment of uveal melanoma

et al. 2021

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide-binding proteins GNAQ/GNA11, and loss of the BRACA1-associated protein 1 (BAP 1). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies.Attempts to utilize the targeted therapies that have been developed for the treatment of other cancers, including a range of signal transduction pathway inhibitors, have rarely produced significant outcomes in UM. Similarly, the application of immunotherapies that are effective in cutaneous melanoma to treat UM have also been disappointing. Other approaches that have been initiated involve proteasomal inhibitors and histone deacetylase inhibitors that are approved for the treatment of other cancers. Nevertheless, there have been occasional positive outcomes from these treatments in UM. Moreover, combination approaches in UM have also yielded some positive developments. It would be valuable to identify how to apply such therapies efficiently in UM, potentially via individualized tumour profiling. It would also be important to characterize UM tumours to differentiate the potential drivers of progression from those in other types of cancers.The recent identification of novel kinases and metastatic genes in UM tumours makes the development of new UM-specific treatments feasible. Accepted ArticleThis article is protected by copyright. All rights reserved A) Uveal Melanoma: Background and risk factors Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and represents ~5 % of melanoma diagnoses in the US annually [1-3]. UM originates from ocular melanocytes with 85% of cases arising from the choroid region and the remainder from the ciliary body and iris [4]. The prognosis in UM is poor, in particular because around 50% of patients develop metastatic disease. Hepatic metastases occur in up to 90% of individuals, followed by metastases in lung and bones, and after establishment of metastatic disease the median survival time is only 4-5 months [5]. At the time of diagnosis, systemic metastases are reported in only 3%of patients, but it is likely that micro-metastases have already developed in many cases [6,7].Currently there are no effective systemic drug therapies for primary or metastatic UM [8,9].The median age at diagnosis is 62 years and the incidence of UM in males and females, and whether there is right or left eye involvement, is similar [10]. Underlying risk factors for UM include melanocytosis, melanocytoma, neurofibromatosis and the presence of atypical nevi [11][12][13][14]. Race is also a significant risk factor with a 150-fold greater incidence in fair-skinned over dark-skinned populations [15]. The incidence of UM in European countries varies wi...

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“…In the last few decades, researchers have focused their attention on the role of lncRNAs in carcinogenesis [ 106 ]. Moreover, lncRNAs were found to be involved in the regulation of a plethora of cancer-related processes in UM [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. Given the important contribution of lncRNAs to cancer progression, their potential application as circulating biomarkers has been investigated.…”

Section: Serum/plasma Circulating Long Rnas In Ummentioning

confidence: 99%

Do Extracellular RNAs Provide Insight into Uveal Melanoma Biology?

Barbagallo

Platania

Drago

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, showing a high mortality due to metastasis. Although it is considered a rare disease, a growing number of papers have reported altered levels of RNAs (i.e., coding and non-coding RNAs) in cancerous tissues and biological fluids from UM patients. The presence of circulating RNAs, whose dysregulation is associated with UM, paved the way to the possibility of exploiting it for diagnostic and prognostic purposes. However, the biological meaning and the origin of such RNAs in blood and ocular fluids of UM patients remain unexplored. In this review, we report the state of the art of circulating RNAs in UM and debate whether the amount and types of RNAs measured in bodily fluids mirror the RNA alterations from source cancer cells. Based on literature data, extracellular RNAs in UM patients do not represent, with rare exceptions, a snapshot of RNA dysregulations occurring in cancerous tissues, but rather the complex and heterogeneous outcome of a systemic dysfunction, including immune system activity, that modifies the mechanisms of RNA delivery from several cell types.

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<p>Long Non-Coding RNA GAS5 Targeting microRNA-21 to Suppress the Invasion and Epithelial–Mesenchymal Transition of Uveal Melanoma</p>

Cited by 16 publications

References 24 publications

Mechanisms of human umbilical cord mesenchymal stem cells-derived exosomal lncRNA GAS5 in alleviating EMT of HPMCs via Wnt/β-catenin signaling pathway

Mechanisms of human umbilical cord mesenchymal stem cells-derived exosomal lncRNA GAS5 in alleviating EMT of HPMCs via Wnt/β-catenin signaling pathway

Development of new therapeutic options for the treatment of uveal melanoma

Do Extracellular RNAs Provide Insight into Uveal Melanoma Biology?

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