Elevated RNA expression of long non-coding HOTAIR promotes cell proliferation and predicts a poor prognosis in patients with diffuse large B cell lymphoma

Abstract

Diffuse large B cell lymphoma (DLBCL) is one of the most common types of malignancy worldwide. The lack of clear symptoms and early detection make it difficult to diagnose at an early stage, leading to poor prognosis of the patients. Long non-coding RNAs (lncRNAs) have come into focus for their important regulatory roles in fundamental biological processes, particularly in cancer initiation, development and progression. The aim of the present study was to investigate the expression of lncRNA Hox transcript antisense intergenic RNA (HOTAIR) in a cohort of patients with DLBCL to assess its clinical value and biological function in DLBCL. The reverse transcription-polymerase chain reaction was used to detect HOTAIR expression levels and cells were transfected with small interfering RNA to compare cell proliferation, cell cycle progression and apoptosis. Western blotting was also conducted to detect possible signaling pathways. It was first found that the expression levels of HOTAIR were upregulated in DLBCL tumor tissues and cell lines, compared with normal tissues and cells. In addition, HOTAIR was significantly correlated with tumor size, clinical stage, B symptoms and International Prognostic Index scores; and higher expression levels of HOTAIR were correlated with improved prognosis. Univariate and multivariate analyses verified that HOTAIR was a key independent predictive factor for DLBCL prognosis. Furthermore, it was revealed that the knockdown of the expression of HOTAIR led to growth inhibition, cell cycle arrest and apoptosis in vitro, possibly through the phosphoinositide 3-kinase/AKT/nuclear factor-κB pathway. These results suggested that HOTAIR may be regarded as a novel indicator of poor prognosis, and may serve as a potential target for gene therapy in the treatment of DLBCL.

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

“…Our results also implied the potential interaction and regulatory loop of p65 and HOTAIR. In line with this, studies have revealed connections between these 2 molecules [35,47,48]. One study demonstrated that HOTAIR positively induced phosphorylation of p65 and activation of NF-κB and that production of HOTAIRinduced tumor necrosis factor alpha (TNF-α) was blocked by the NF-κB inhibitor.…”

“…This finding suggested that NF-κB/p65 was involved in the production of HOTAIR-induced TNF-α in cardiomyocytes in a lipopolysaccharide-induced mouse model [47]. In addition, knockdown of HOTAIR inhibited growth and induced cell cycle arrest and apoptosis in vitro partly via the NF-κB signaling pathways in large B cell lymphoma cells [48]. Our findings provided a novel insight into the relation between NF-κB/p65 and HOTAIR affected by PPI, as well as emphasized the tumor promoter roles of NF-κB/p65 and HOTAIR involved in the anti-tumor effects of PPI.…”

Long non‐coding RNA DBH‐AS1 promotes cancer progression in diffuse large B‐cell lymphoma by targeting FN1 via RNA‐binding protein BUD13

“…The roles of lncRNAs in DLBC progression have been verified in a great number of researches. For instance, HOTAIR would promote the proliferation of DLBC cells while predicting poor prognosis of DLBC patients (Yan et al, 2016). HULC was also found to represent pro‐oncogenic activity of DLBC (Peng et al, 2016).…”

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

“…A study showed that high HOTAIR expression in DLBCL tumor tissues and cells was strongly correlated with tumor size, clinical stage, symptoms, and prognostic index scores. Moreover, silencing of HOTAIR inhibited growth, induced cell cycle arrest, and apoptosis via the PI3K/Akt/NF-κB pathways, suggesting that HOTAIR can be used as a novel marker and potential target for gene therapy in the treatment of DLBCL [144]. Imatinib, a breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitor, has been used to treat chronic myelogenous leukemia (CML) [145].…”