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The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells.
Gynecol Oncol. 2015 Apr; 137(1):143-51.GO

Abstract

OBJECTIVE

Ovarian cancer is the deadliest gynaecological cancer. A major contributor to the poor survival rate is the development of chemoresistance to platinum-based therapies such as cisplatin and carboplatin. Here we aimed to test the role of miRNAs in the acquisition of drug resistance in ovarian cancer.

METHODS

We used microarrays to measure miRNA levels in the ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. The role of miRNAs and the mRNA targets were tested using transfected miRNA mimics and siRNAs, respectively. Potential in vivo significance was investigated by analysing RNA levels in cohorts of ovarian cancer patients.

RESULTS

We identified several miRNAs that are increased in cisplatin-resistant cells. We show that most of these do not directly contribute to cisplatin resistance. Interestingly, miR-21-3p, the passenger strand of the known oncomiR, directed increased resistance to cisplatin in a range of ovarian cell lines. This effect was specific to the star strand, as miR-21-5p had the opposite effect and actually increased sensitivity of A2780 cells to cisplatin. We identify NAV3 as a potential target of miR-21-3p and show that knockdown of NAV3 increases resistance. Exosomes released by CP70 cells were also capable of increasing resistance in A2780 cells, although this was independent of miR-21-3p. Finally, we use publically available transcriptomic data to demonstrate that miR-21-3p is raised, while NAV3 is reduced, in ovarian tumours that are resistant to platinum treatment.

CONCLUSION

Our data suggest that miR-21-3p can induce cisplatin resistance in ovarian tumours, potentially by targeting the NAV3 gene.

Authors+Show Affiliations

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK.Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford, OX3 0BP, UK. Electronic address: dcarter@brookes.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25579119

Citation

Pink, Ryan Charles, et al. "The Passenger Strand, miR-21-3p, Plays a Role in Mediating Cisplatin Resistance in Ovarian Cancer Cells." Gynecologic Oncology, vol. 137, no. 1, 2015, pp. 143-51.
Pink RC, Samuel P, Massa D, et al. The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol. 2015;137(1):143-51.
Pink, R. C., Samuel, P., Massa, D., Caley, D. P., Brooks, S. A., & Carter, D. R. (2015). The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecologic Oncology, 137(1), 143-51. https://doi.org/10.1016/j.ygyno.2014.12.042
Pink RC, et al. The Passenger Strand, miR-21-3p, Plays a Role in Mediating Cisplatin Resistance in Ovarian Cancer Cells. Gynecol Oncol. 2015;137(1):143-51. PubMed PMID: 25579119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. AU - Pink,Ryan Charles, AU - Samuel,Priya, AU - Massa,Davide, AU - Caley,Daniel Paul, AU - Brooks,Susan Ann, AU - Carter,David Raul Francisco, Y1 - 2015/01/08/ PY - 2014/10/09/received PY - 2014/12/19/revised PY - 2014/12/29/accepted PY - 2015/1/13/entrez PY - 2015/1/13/pubmed PY - 2015/5/29/medline KW - Cisplatin KW - Exosome KW - Ovarian cancer KW - Resistance KW - miRNA SP - 143 EP - 51 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 137 IS - 1 N2 - OBJECTIVE: Ovarian cancer is the deadliest gynaecological cancer. A major contributor to the poor survival rate is the development of chemoresistance to platinum-based therapies such as cisplatin and carboplatin. Here we aimed to test the role of miRNAs in the acquisition of drug resistance in ovarian cancer. METHODS: We used microarrays to measure miRNA levels in the ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. The role of miRNAs and the mRNA targets were tested using transfected miRNA mimics and siRNAs, respectively. Potential in vivo significance was investigated by analysing RNA levels in cohorts of ovarian cancer patients. RESULTS: We identified several miRNAs that are increased in cisplatin-resistant cells. We show that most of these do not directly contribute to cisplatin resistance. Interestingly, miR-21-3p, the passenger strand of the known oncomiR, directed increased resistance to cisplatin in a range of ovarian cell lines. This effect was specific to the star strand, as miR-21-5p had the opposite effect and actually increased sensitivity of A2780 cells to cisplatin. We identify NAV3 as a potential target of miR-21-3p and show that knockdown of NAV3 increases resistance. Exosomes released by CP70 cells were also capable of increasing resistance in A2780 cells, although this was independent of miR-21-3p. Finally, we use publically available transcriptomic data to demonstrate that miR-21-3p is raised, while NAV3 is reduced, in ovarian tumours that are resistant to platinum treatment. CONCLUSION: Our data suggest that miR-21-3p can induce cisplatin resistance in ovarian tumours, potentially by targeting the NAV3 gene. SN - 1095-6859 UR - https://www.unboundmedicine.com/medline/citation/25579119/The_passenger_strand_miR_21_3p_plays_a_role_in_mediating_cisplatin_resistance_in_ovarian_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(15)00004-9 DB - PRIME DP - Unbound Medicine ER -