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.

• Authors: Shudan Mao, Jieping Jin, Zhe Li, Wenqi Yang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 23 Issue 2 (02 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 33325535 (Publication Type: Journal Article)

Chemical References

• BAX protein, human
• CDKN1A protein, human
• CDKN2B antisense RNA, human
• Cyclin-Dependent Kinase Inhibitor p21
• E2F1 Transcription Factor
• RNA, Long Noncoding
• TGFB1 protein, human
• Transforming Growth Factor beta1
• bcl-2-Associated X Protein
• Cyclin D1

Topics

• Apoptosis
• Burkitt Lymphoma (genetics, metabolism, physiopathology)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (genetics)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• E2F1 Transcription Factor (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• RNA, Long Noncoding (genetics, metabolism, physiology)
• Signal Transduction
• Transforming Growth Factor beta1 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics)