Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chemoresistance is the main obstacle of treatment in patients with
osteosarcoma
. RNA-binding protein PTBP1 has been identified as an oncogene in various cancers. However, the role of PTBP1 in
osteosarcoma
, especially in chemoresistant
osteosarcoma
, and the underlying mechanism remain unclear. In this study, we aimed to explore the functions of PTBP1 in chemoresistance of
osteosarcoma
. We found that PTBP1 was significantly increased in chemotherapeutically insensitive
osteosarcoma
tissues and cisplatin-resistant
osteosarcoma
cell lines (MG-63
CISR
and U-2OS
CISR
) as compared to chemotherapy-sensitive
osteosarcoma
tissues and cell lines. Knock-down of PTBP1 can enhance the anti-proliferation and apoptosis-induced effects of cisplatin in MG-63
CISR
and U-2OS
CISR
cells. Moreover, PTBP1 knock-down significantly up-regulated the expression of the copper transporter
SLC31A1
, as indicated by transcriptome sequencing. Through RNA immunoprecipitation, dual-luciferase reporter assay and RNA stability detection, we confirmed that PTBP1 binds to
SLC31A1
mRNA and regulates the expression level of
SLC31A1
by affecting mRNA stability. Additionally,
SLC31A1
silencing abrogated the chemosensitizing effect of PTBP1 knock-down in MG-63
CISR
and U-2OS
CISR
cells. Using a nude mouse xenograft model, we further confirmed that PTBP1 knock-down enhanced chemoresistant
osteosarcoma
responsiveness to cisplatin treatment in vivo. Collectively, the present study suggests that PTBP1 is a crucial determinant of chemoresistance in
osteosarcoma
.
...
PMID:PTBP1 modulates osteosarcoma chemoresistance to cisplatin by regulating the expression of the copper transporter SLC31A1. 3220 35
