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RETRACTED: A Novel Mechanism of Doxorubicin Resistance and Tumorigenesis Mediated by MicroRNA-501-5p-Suppressed BLID
- Source :
- Molecular Therapy. Nucleic Acids, Molecular Therapy: Nucleic Acids, Vol 12, Iss, Pp 578-590 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood. In this study, we identified that BLID (BH3-like motif-containing protein, cell death inducer) was directly regulated by miR-501 at the post-transcriptional level in multiple gastric cancer cell lines. Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR-501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin, and enhanced cell proliferation, migration, and invasion. Subcutaneous injection of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of xenograft tumors and resistance to doxorubicin treatment, unlike injection of negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least partially by directly targeting BLID and subsequent inactivation of caspase-9 and caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin resistance and enhances the tumorigenesis of gastric cancer cells by suppressing BLID. miR-501 might be a potential target for doxorubicin resistance and gastric cancer therapy. Keywords: microRNA-501-5p, chemoresistance, doxorubicin, BLID, gastric cancer
- Subjects :
- microRNA-501-5p
0301 basic medicine
Anthracycline
medicine.disease_cause
doxorubicin
Article
03 medical and health sciences
0302 clinical medicine
Drug Discovery
medicine
Doxorubicin
Protein kinase B
BLID
Chemistry
Cell growth
gastric cancer
lcsh:RM1-950
chemoresistance
Cancer
medicine.disease
lcsh:Therapeutics. Pharmacology
030104 developmental biology
Apoptosis
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Molecular Medicine
Carcinogenesis
medicine.drug
Subjects
Details
- ISSN :
- 21622531
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy - Nucleic Acids
- Accession number :
- edsair.doi.dedup.....6a706292b95f6c981a54112c6dbb6249