Abstract
The present study was directed toward laying new findings for Extranodal natural killer/T-cell lymphoma (ENKL)-oriented therapy with a focus on long non-coding RNA (lncRNA)–microRNAs (miRNAs)–mRNA interaction. The expression and function of XIST (X-inactive specific transcript) were analyzed both in vivo and in vitro. The online database of lncRNA-miRNA interaction was used to screen the target of XIST, and miR-497 was selected. Next, the predicted binding between XIST and miR-497, and the dynamic effect of XIST and miR-497 on downstream Bcl-w was evaluated. We found that XIST dramatically increased in the blood of ENKL patients and cell lines. XIST knockdown suppressed the cell proliferation and migration in vivo and in vitro. Herein, we confirmed the negative interaction between XIST and miR-497. Moreover, XIST knockdown reduced the protein levels of Bcl-w, a downstream target of miR-497. XIST sponges miR-497 to promote Bcl-w expression, and finally modulating ENKL cell proliferation and migration. To be interested, inhibition of Bcl-w by ABT737 can overcome the high expression of XIST, and suppressed the ENKL proliferation and migration by inducing apoptosis. This study provided a novel experimental basis for ENKL-oriented therapy with a focus on the lncRNA–miRNA–mRNA interaction.
Highlights
Non-Hodgkin’s lymphoma (NHL) stems from B, T, and natural killer (NK) lymphocytes and comprises both indolent and aggressive types (Swerdlow et al, 2016)
The findings demonstrated that XIST expression was notably upregulated in Extranodal natural killer/T-cell lymphoma (ENKL) patients (Figure 1A)
XIST expression was dramatically augmented in ENKL cells, which was consistent with its high expression in the tissue samples (Figure 1D)
Summary
Non-Hodgkin’s lymphoma (NHL) stems from B, T, and natural killer (NK) lymphocytes and comprises both indolent and aggressive types (Swerdlow et al, 2016). Extranodal NK/T-cell lymphoma (ENKL), nasal type, is an aggressive NHL representing a rare specific extranodal subtype of peripheral T-cell lymphoma (PTCL) (Tse and Kwong, 2017). ENKL occurs mainly (80%) in the nose, and upper aerodigestive tract, with only a small proportion (20%) observed in non-nasal lncRNA–miRNA–mRNA Interaction areas (Au et al, 2009). ENKL is an aggressive lymphoma with poor survival in an untreated patient measured in weeks to months; the median overall survival is 3 years for localized disease and 8 months for metastatic disease (Lee et al, 2006). There is no single standard of care for the treatment of ENKL. New molecular targeted therapies are required for the treatment of ENKL malignancies
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