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Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells.
- Source :
-
Cell death & disease [Cell Death Dis] 2019 Oct 10; Vol. 10 (10), pp. 764. Date of Electronic Publication: 2019 Oct 10. - Publication Year :
- 2019
-
Abstract
- Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.
- Subjects :
- Animals
Breast Neoplasms genetics
Breast Neoplasms radiotherapy
Cell Line, Tumor
Checkpoint Kinase 1 genetics
Female
Gene Expression Regulation, Neoplastic genetics
Gene Expression Regulation, Neoplastic radiation effects
Humans
Mass Spectrometry
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs genetics
Oligonucleotide Array Sequence Analysis
RNA, Long Noncoding genetics
RNA, Small Interfering
Radiation Tolerance radiation effects
Radiation-Sensitizing Agents therapeutic use
Transplantation, Heterologous
Ubiquitin metabolism
Ubiquitin-Specific Peptidase 7 genetics
Ubiquitin-Specific Peptidase 7 metabolism
Breast Neoplasms metabolism
Checkpoint Kinase 1 metabolism
MicroRNAs metabolism
RNA, Long Noncoding metabolism
Radiation Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 31601781
- Full Text :
- https://doi.org/10.1038/s41419-019-1996-0