The long non-coding RNA PARTICLE is associated with WWOX and the absence of FRA16D breakage in osteosarcoma patients

Abstract

Breakage of the fragile site FRA16D disrupts the WWOX (WW Domain Containing Oxidoreductase) tumor suppressor gene in osteosarcoma. However, the frequency of breakage is not sufficient to explain the rate of WWOX loss in pathogenesis. The involvement of non-coding RNA transcripts is proposed due to their accumulation at fragile sites, where they are advocated to influence specific chromosomal regions associated with malignancy. The long ncRNA PARTICLE (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA) is transiently elevated in response to irradiation and influences epigenetic silencing modification within WWOX. It now emerges that elevated PARTICLE levels are significantly associated with FRA16D non-breakage in OS patients. Although not associated with overall survival, high PARTICLE levels were found to be significantly linked to metastasis free outcome. The transcription of both PARTICLE and WWOX are transiently responsive to exposure to low doses of radiation in osteosarcoma cell lines. Herein, a relationship between WWOX and PARTICLE transcription is suggested in human osteosarcoma cell lines representing alternative genetic backgrounds. PARTICLE over-expression ameliorated WWOX promoter activity in U2OS harboring FRA16D non-breakage. It can be concluded that the lncRNA PARTICLE influences the WWOX tumor suppressor and in the absence of WWOX FRA16D breakage, it is associated with OS metastasis-free survival.

Long noncoding RNA DNAJC3‐AS1 promotes osteosarcoma progression via its sense‐cognate gene DNAJC3

“…Owing to their various functions in the pathogenesis of diseases, lncRNAs have been widely studied in different types of tumors . Among the diverse kinds of lncRNAs, antisense lncRNAs attract more and more investigations.…”

“…Osteosarcoma (OS) is the most common primary solid bone malignancy threatening health of children and adolescence . On account of lacking effective diagnostic methods in clinic, OS patients present high rate (approximately 20%) of lung metastases at first diagnosis .…”

PARTICLE − The RNA podium for genomic silencers

“…Indeed, others have identified radiation sensitive up‐regulated lncRNAs such as lincRNA‐p21 (long intergenic non‐coding RNA‐p21), GAS5 (growth arrest‐specific 5), PANDA (p21 associated ncRNA DNA damage‐activated; PANDAR ), and ANRIL (antisense non‐coding RNA in the INK4 locus; CDKN2B‐AS1 ) but as part of a DNA damage response to high‐dose exposure levels (Hung et al, ; J. R. Hall et al, ; Ozgur et al, ). Subsequently, PARTICLE expression was confirmed as a ubiquitous tissue responder to LDR but with its higher levels of expression in malignant tissue compared to healthy control counterparts (O'Leary et al, ; O'Leary, Maugg et al, ).…”

Abnormally expressed long non-coding RNAs in prognosis of Osteosarcoma: A systematic review and meta-analysis

“…According to the inclusion and exclusion criteria, the full texts of remaining 113 articles were read for further evaluation and then 93 articles were excluded. Finally, 20 studies were included in the meta-analysis [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44].

Fig. 1Flow diagram of study selection process.

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“…2, the heterogeneity test indicated the existence of medium heterogeneity in OS (I 2 = 54%, P < 0.00001), the pooled HR was 2.16 (95% CI: 1.68–2.79), which was calculated using random-effects model, the results suggested that a high LncRNA expression was significantly correlated with the poorer OS prognosis. The increased expressions of LncRNA UCA1 [25,38], XIST [26], SOX2-OT [28], MALAT1 [29,36], HNF1A-AS1 [30], PARTICLE [31], CCAL [32], 91H [33], HULC [34,43], BCAR4 [35,39], TUG1 [40], BANCR [41], MEG3 [42] and HOTTIP [44] indicated poorer prognoses of OS, on the contrary, the decreased expressions LncRNA DANCR [27] and TUSC7 [37] indicated better prognoses of OS. A total of 2 studies, including 185 patients, were included in the assessment of the effect of LncRNA expression on DFS (Fig.…”