PMID- 34717683
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220128
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 16
IP  - 1
DP  - 2021 Oct 30
TI  - Doxorubicin inhibits osteosarcoma progression by regulating circ_0000006/miR-646/ 
      BDNF axis.
PG  - 645
LID - 10.1186/s13018-021-02782-y [doi]
LID - 645
AB  - BACKGROUND: Osteosarcoma (OS) is the most common aggressive bone tumor in 
      children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This 
      study aims to reveal the effects and underneath mechanism of DOX treatment in OS 
      progression. METHODS: The expression of circular_0000006 (circ_0000006), 
      microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected 
      by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein 
      expression was determined by western blot. Cell proliferation was illustrated by 
      cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and 
      invasion were revealed by transwell migration and wound-healing assays and 
      transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow 
      cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF 
      was predicted by circRNA interactome and targetscan online database, 
      respectively, and verified by dual-luciferase reporter assay. The effects of 
      circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor 
      formation assay. RESULTS: Circ_0000006 expression and the mRNA and protein levels 
      of BDNF were dramatically upregulated, and miR-646 expression was effectively 
      downregulated in OS tissues or cells compared with control groups. Circ_0000006 
      expression and BDNF protein expression were lower, and miR-646 expression was 
      higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 
      knockdown repressed cell proliferation, migration and invasion, whereas promoted 
      cell apoptosis under DOX treatment in OS cells; however, these effects were 
      attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to 
      bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo. CONCLUSION: 
      Circ_0000006 knockdown promoted DOX-mediated effects on OS development by 
      miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.
CI  - (c) 2021. The Author(s).
FAU - Amuti, Abulimiti
AU  - Amuti A
AD  - Department of Orthopaedics, The Second Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, Xinjiang, China.
FAU - Liu, Dehu
AU  - Liu D
AD  - Department of Osteology, Tai'an Traditional Chinese Medicine Hospital, Taian, 
      Shandong, China.
FAU - Maimaiti, Ayiguli
AU  - Maimaiti A
AD  - Department of Orthopaedics, The Second Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, Xinjiang, China.
FAU - Yu, Yao
AU  - Yu Y
AD  - Six Subjects of Hand Surgery, Affiliated Central Hospital of Shenyang Medical 
      College, Shenyang, Liaoning, China.
FAU - Yasen, Yalikun
AU  - Yasen Y
AD  - Department of Orthopaedics, The Second Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, Xinjiang, China.
FAU - Ma, Haoguang
AU  - Ma H
AD  - Department of Surgery, Hot Spring Sanatorium of Linyi, Linyi Hedong Central 
      Hospital, Linyi, Shandong, China.
FAU - Li, Rui
AU  - Li R
AD  - Department of Joint Surgery, The Fourth Hospital of Baotou, Baotou City, 
      Mongolia, China.
FAU - Deng, Shurong
AU  - Deng S
AD  - Department of Pharmacy, The First Affiliated Hospital of Jinan University, 
      Guangzhou, Guangdong, China.
FAU - Pang, Fei
AU  - Pang F
AD  - Department of Orthopaedics, Shaoxing People's Hospital, No. 568 North Zhongxing 
      Road, Yuecheng District, Shaoxing City, 312000, Zhejiang Province, China. 
      jrxvtw@163.com.
FAU - Tian, Youliang
AU  - Tian Y
AD  - Department of Rehabilitation Medicine and Physiotherapy, PLA Strategic Support 
      Force Characteristic Medical Center, No. 9 Anxiang North Lane, Chaoyang District, 
      , Beijing, 100101, China. epeqyf@163.com.
LA  - eng
PT  - Journal Article
DEP - 20211030
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MIRN646 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Disease Progression
MH  - Doxorubicin/pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/genetics
MH  - *Osteosarcoma/drug therapy/genetics
MH  - RNA, Circular
PMC - PMC8557021
OTO - NOTNLM
OT  - BDNF
OT  - DOX
OT  - Osteosarcoma
OT  - circ_0000006
OT  - miR-646
COIS- The authors declare that they have no competing interests.
EDAT- 2021/11/01 06:00
MHDA- 2022/01/29 06:00
PMCR- 2021/10/30
CRDT- 2021/10/31 20:36
PHST- 2021/01/21 00:00 [received]
PHST- 2021/10/06 00:00 [accepted]
PHST- 2021/10/31 20:36 [entrez]
PHST- 2021/11/01 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/10/30 00:00 [pmc-release]
AID - 10.1186/s13018-021-02782-y [pii]
AID - 2782 [pii]
AID - 10.1186/s13018-021-02782-y [doi]
PST - epublish
SO  - J Orthop Surg Res. 2021 Oct 30;16(1):645. doi: 10.1186/s13018-021-02782-y.