Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis

Immunity & Ageing

Cui Zhang¹  Yonghua Yao¹  Jinfeng Sao¹  Min Chu¹  Yingchao Fan¹  Xiaoyan Ma¹  Liting Wu¹  Wenfang Zhuang¹ 

[1] Medical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and Technology, 999 Shiguang Road, Yangpu District, 200438, Shanghai, China;

关键词: Multiple myeloma;    BDNF-AS;    miR-125a-5p;    miR-125b-5p;    Bcl-2;    Proliferation;   

DOI  :  10.1186/s12979-021-00258-5

来源: Springer

【 摘 要 】

PurposeThis study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM).MethodsThe expression of BDNF-AS, miR-125a-5p, and miR-125b-5p in MM serum and cell lines were detected by quantitative reverse transcriptase PCR (qRT-PCR). The binding relationships between miR-125a/b-5p and BDNF-AS or Bcl-2 were predicted by Starbase and verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining assay. Cell migration was evaluated by wound healing assay. The expression levels of apoptosis-related proteins were evaluated by Western blot analysis. The role of BDNF-AS was also investigated in a xenograft tumor model in vivo.ResultsBDNF-AS was significantly upregulated, while miR-125a-5p and miR-125b-5p were downregulated in MM serum and corresponding cancer cell lines. Knockdown of BDNF-AS effectively inhibited the proliferation and migration of MM.1S and U266 cells, and co-transfection of miR-125a-5p or miR-125b-5p inhibitor and sh-BDNF-AS enhanced cell proliferation and migration compared with that in sh-BDNF-AS group. Knockdown of miR-125a-5p or miR-125b-5p significantly enhanced the proliferation and migration of MM.1S and U266 cells, and co-transfection of sh-Bcl-2 and miR-125a/b-5p inhibitor inhibited cell proliferation compared with that in miR-125a/b-5p inhibitor group. Moreover, knockdown of BDNF-AS increased the expression levels of apoptosis-related proteins (cleaved caspase 3 and cleaved PARP), while knockdown of miR-125a-5p or miR-125b-5p reduced the expression levels of these apoptosis-related proteins compared with knockdown of BDNF-AS. Furthermore, knockdown of BDNF-AS effectively suppressed MM tumor growth in vivo.ConclusionOur findings revealed that knockdown of BDNF-AS inhibited the progression of MM by targeting the miR-125a/b-5p-Bcl-2 axis, indicating that BDNF-AS might serve as a novel drug target for MM.

【 授权许可】

CC BY