Knockdown of long non‑coding RNA ANRIL inhibits the proliferation and promotes the apoptosis of Burkitt lymphoma cells through the TGF‑β1 signaling pathway

Abstract

Burkitt lymphoma (BL) has a high mortality rate and its treatment is currently limited to chemotherapy combined with immunotherapy. The long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) has been identified as an oncogene that can regulate cell proliferation and apoptosis in multiple types of cancer. However, the function of ANRIL in BL remains unknown. The present study aimed to determine the effect of ANRIL on cell proliferation and apoptosis in BL. Reverse transcription-quantitative PCR was used to analyze the expression levels of ANRIL in BL cells. The effect of ANRIL knockdown on BL cells was determined using Cell Counting Kit-8, flow cytometric, western blotting, immunofluorescence staining and Hoechst staining assays. The results revealed that ANRIL silencing inhibited the proliferation and promoted the apoptosis of BL cells. In addition, the expression levels of cyclin D1, E2F transcription factor 1 and Bcl-2 were downregulated, while the expression levels of cyclin-dependent kinase inhibitor 1A, Bcl-2-associated X protein, cleaved-caspase-9/pro-caspase-9 and cleaved-caspase-3/pro-caspase-3 were upregulated. Furthermore, the knockdown of ANRIL activated the TGF-β1 signaling pathway, as evidenced by the upregulated expression levels of TGF-β1, phosphorylated (p)-SMAD2/3/SMAD2/3, p-SMAD1/SMAD1 and sphingosine-1-phosphate receptor 2. Moreover, the protective effect of ANRIL silencing in BL could be inhibited by the TGF-β receptor type I/II dual inhibitor, LY2109761. In conclusion, the findings of the present study suggested that the knockdown of ANRIL may inhibit cell proliferation and promote cell apoptosis in BL by regulating the TGF-β1 signaling pathway, which may provide a novel target for the treatment of BL.

MicroRNA and Other Non-Coding RNAs in Epstein–Barr Virus-Associated Cancers

“…Long non-coding RNA, plasmacytoma variant translocation 1 (PVT1) has also been reported to be associated with MYC expression as well as with alterations in cell cycle-associated genes in the Raji cell line [117]. The antisense non-coding RNA in the INK4 locus (ANRIL) is another lncRNA that has been identified as a regulator of cell proliferation and apoptosis in multiple types of cancer, including BL, and does so by regulating TGF-β1 signaling [118]. LncRNA-ANRIL also promotes gastric cancer progression by enhancing NF-κB signaling [119] and regulates STAT3 in liver cancer [120].…”

Allelic and Genotypic Analysis of LncRNA ANRIL rs4977574 A/G Mutations in Oral Squamous Cell Carcinoma Patients: Insights into Tumor Characteristics and Genotypic Correlations

“…The positive impact of lncRNA ANRIL on the proliferation of cancer cells is suggested to be mediated via multiple mechanisms, including the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/Akt) pathway [ 29 ], transforming growth factor- β /Suppressor of mothers against decapentaplegic (TGF- β /Smad) pathway [ 12 ], and suppression of p14 ARF [ 30 ], and p15INK4B [ 31 ]. Moreover, the knockdown of lncRNA ANRIL could result in cell cycle arrest in the G1 phase of the cell cycle [ 32 ]. The antiapoptotic effect of lncRNA ANRIL is shown to be mediated via TGF- β 1 signaling pathway [ 12 , 32 ].…”

“…Moreover, the knockdown of lncRNA ANRIL could result in cell cycle arrest in the G1 phase of the cell cycle [ 32 ]. The antiapoptotic effect of lncRNA ANRIL is shown to be mediated via TGF- β 1 signaling pathway [ 12 , 32 ]. Worth mentioning, some of the cell proteins that are highly involved in cell apoptosis, such as Bcl-2, caspase-3, and caspase-9 are affected by the level of expression of lncRNA ANRIL [ 32 ].…”

“…The antiapoptotic effect of lncRNA ANRIL is shown to be mediated via TGF- β 1 signaling pathway [ 12 , 32 ]. Worth mentioning, some of the cell proteins that are highly involved in cell apoptosis, such as Bcl-2, caspase-3, and caspase-9 are affected by the level of expression of lncRNA ANRIL [ 32 ]. Therefore, lncRNA ANRIL seems to exert an imperative role in the cancer progression.…”

Roles of TGF‑β signalling pathway‑related lncRNAs in cancer (Review)

“…In lymphoma, knockdown of lncRNA ANRIL may inhibit proliferation and promote apoptosis of Burkitt's lymphoma cells by regulating the TGF-β1 signalling pathway ( 109 ).…”