Abstract
BackgroundNONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood.MethodsFISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry.ResultsThe expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N6-methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN.ConclusionsTRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.
Highlights
Non-POU domain containing octamer binding (NONO)-Transcription factor binding to IGHM enhancer 3 (TFE3) translocation renal cell carcinoma (NONO-TFE3 Translocation renal cell carcinoma (tRCC)) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs)
TRAF3IP2‐AS1 expression is significantly decreased in NONO‐TFE3 tRCCIn our previous study, TRAF2IP2-AS1 was identified as a potential target gene of NONO-TFE3 by ChIPseq [16]
To explore if TRAF3IP2-AS1 expression was linked to NONO-TFE3 tRCC, the expression and distribution of TRAF3IP2-AS1 were detected by Fluorescence in situ hybridization (FISH)
Summary
NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood. Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), known as transcription factor binding to IGHM enhancer 3 (TFE3)-fusion associated RCC, is recently stratified in the MiT (microphthalmia transcription factor) family tRCC as a new subset of RCC in the. Xp11.2 tRCC, which features TFE3 fusion gene and poor prognosis of patients, is caused by several different translocations involving chromosome TFE3 with partner genes, including ASPL, PRCC,NONO and CLTC, as well as some other housekeeping genes [2,3,4,5,6]. The potential molecular mechanism of lncRNAs associated with the oncogenesis of Xp11.2 tRCC is still unclear
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