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NAD(P)H:quinone oxidoreductase 1 determines radiosensitivity of triple negative breast cancer cells and is controlled by long non-coding RNA NEAT1.
- Source :
-
International journal of medical sciences [Int J Med Sci] 2020 Aug 19; Vol. 17 (14), pp. 2214-2224. Date of Electronic Publication: 2020 Aug 19 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Radioresistant cells cause recurrence in patients with breast cancer after they undergo radiation therapy. The molecular mechanisms by which cancer cells obtain radioresistance should be understood to develop radiation-sensitizing agents. Results showed that the protein expression and activity of NAD(P)H:quinone oxidoreductase 1 (NQO1) were upregulated in radioresistant MDA-MB-231 triple-negative breast cancer (TNBC) cells. NQO1 knockdown inhibited the proliferation of NQO1 expressing Hs578t TNBC cells or the radioresistant MDA-MB-231 cells, whereas NOQ1 overexpression increased the survival of MDA-MB-231 cells, which lack of NQO1 expression originally, under irradiation. The cytotoxicity of β-lapachone, an NQO1-dependent bioactivatable compound, was greater in radioresistant MDA-MB-231 cells than in parental cells. β-lapachone displayed a radiosensitization effect on Hs578t or radioresistant MBDA-MB-231 cells. The expression of the long noncoding RNA NEAT1 positively regulated the NQO1 expression in radioresistant MDA-MB-231 cells at a translational level rather than at a transcription level. The inhibition of the NEAT1 expression through the CRISPR-Cas9 method increased the sensitivity of radioresistant MDA-MB-231 cells to radiation and decreased their proliferation, the activity of cancer stem cells, and the expression of stemness genes, including BMI1, Oct4, and Sox2. In conclusion, the NQO1 expression in triple-negative breast cancer cells determined their radiosensitivity and was controlled by NEAT1. In addition, NOQ1 bioactivatable compounds displayed potential for application in the development of radiation sensitizers in breast cancer.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Cell Line, Tumor
Cell Proliferation genetics
Cell Proliferation radiation effects
Cell Survival genetics
Cell Survival radiation effects
Female
Gene Expression Regulation, Neoplastic radiation effects
Gene Knockdown Techniques
Humans
NAD(P)H Dehydrogenase (Quinone) metabolism
Naphthoquinones pharmacology
Neoplastic Stem Cells drug effects
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells radiation effects
RNA, Long Noncoding genetics
Radiation-Sensitizing Agents pharmacology
Triple Negative Breast Neoplasms genetics
Triple Negative Breast Neoplasms pathology
NAD(P)H Dehydrogenase (Quinone) genetics
RNA, Long Noncoding metabolism
Radiation Tolerance genetics
Triple Negative Breast Neoplasms radiotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1449-1907
- Volume :
- 17
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- International journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32922184
- Full Text :
- https://doi.org/10.7150/ijms.45706