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

Abstract Purpose This study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM). Methods The 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...

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Main Authors: Min Chu, Yingchao Fan, Liting Wu, Xiaoyan Ma, Jinfeng Sao, Yonghua Yao, Wenfang Zhuang, Cui Zhang
Format: Article
Language:English
Published: BMC 2022-01-01
Series:Immunity & Ageing
Subjects:
Online Access:https://doi.org/10.1186/s12979-021-00258-5
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author Min Chu
Yingchao Fan
Liting Wu
Xiaoyan Ma
Jinfeng Sao
Yonghua Yao
Wenfang Zhuang
Cui Zhang
author_facet Min Chu
Yingchao Fan
Liting Wu
Xiaoyan Ma
Jinfeng Sao
Yonghua Yao
Wenfang Zhuang
Cui Zhang
author_sort Min Chu
collection DOAJ
description Abstract Purpose This study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM). Methods The 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. Results BDNF-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. Conclusion Our 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.
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spelling doaj.art-30c713b6bf344306beafc613f0602aa62022-12-21T17:49:26ZengBMCImmunity & Ageing1742-49332022-01-0119111710.1186/s12979-021-00258-5Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axisMin Chu0Yingchao Fan1Liting Wu2Xiaoyan Ma3Jinfeng Sao4Yonghua Yao5Wenfang Zhuang6Cui Zhang7Medical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyMedical laboratory, Shidong Hospital Affiliated to University of Shanghai For Science and TechnologyAbstract Purpose This study aimed to explore the role of long non-coding RNA (lncRNA) BDNF-AS in the progression of multiple myeloma (MM). Methods The 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. Results BDNF-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. Conclusion Our 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.https://doi.org/10.1186/s12979-021-00258-5Multiple myelomaBDNF-ASmiR-125a-5pmiR-125b-5pBcl-2Proliferation
spellingShingle Min Chu
Yingchao Fan
Liting Wu
Xiaoyan Ma
Jinfeng Sao
Yonghua Yao
Wenfang Zhuang
Cui Zhang
Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
Immunity & Ageing
Multiple myeloma
BDNF-AS
miR-125a-5p
miR-125b-5p
Bcl-2
Proliferation
title Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
title_full Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
title_fullStr Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
title_full_unstemmed Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
title_short Knockdown of lncRNA BDNF-AS inhibited the progression of multiple myeloma by targeting the miR-125a/b-5p-BCL2 axis
title_sort knockdown of lncrna bdnf as inhibited the progression of multiple myeloma by targeting the mir 125a b 5p bcl2 axis
topic Multiple myeloma
BDNF-AS
miR-125a-5p
miR-125b-5p
Bcl-2
Proliferation
url https://doi.org/10.1186/s12979-021-00258-5
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