Document Type : Original Article
Authors
1 Clinical Fellowship, Department of Orthopedic and Traumatology, Universitätsklinikum Bonn, Bonn, Germany
2 Department of Orthopedic and Traumatology, Universitätsklinikum Bonn, Bonn, Germany
3 Department of Genetics, Faculty of Life Science, Azad University of Tehran Medical Sciences Branch, Tehran, Iran
4 Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran
5 Department of Radiology, Zahedan University of Medical Science, Zahedan, Iran
Abstract
Introduction: MicroRNA-124 (miR-124) is moderated in some human malignancies and is associated with tumor advancement. But, its expression and clinical importance in ovarian carcinoma is still unclear. Thus, the goal of this study was to feature the clinical importance of personalized miR-124 expression in ovarian carcinoma. Methods: 94 women ovarian cancer tissues and 26 normal ovarian tissues were accumulated from patients. We used Real-time PCR to quantify the expression of personalized miR-124 in clinical ovarian carcinoma specimen and normal tissues. Moreover, we measured the miR-124 relationship with clinicopathologic characteristics and the ovarian carcinoma survival. Results: The lesser expression of miR-124 in tumor tissues can be found in compared with normal tissue using PCR method (P < 0.05). Our data exhibited that there is a notable association among low expression of miR-12 and clinical staging of ovarian carcinoma (P = 0.023). Nevertheless, miR-124 expression was not notably associated with age (P = 0. 671), differentiation status (P = 0.512), lymph node metastasis (P = 0.415) and histological subtypes (0.547). Kaplan-Meier survival analysis and log-rank test were applied in present study. These tests showed the less expression on patients had markedly short-term survival time in comparison with high expression group (P = 0.022). Multivariate Cox proportional hazards model analysis revealed that less expression of miR-124 and clinical staging were contribute to short-term survival in patients with ovarian carcinoma. The HR of the low miR-124 expression group was calculated to be 2.532 (95% CI: 1.572-9.237, P = 0.021), (clinical staging HR: 2.532; 95% CI: 1.321-9.241, P = 0.032).
Conclusions: These findings suggested that personalized miR-124 could be considered as an independent prognostic factor for ovarian carcinoma patients. Our findings suggested that low expression of personalized miR-124 has prognostic worthiness in ovarian.
Keywords
2012;2(1):1-14. doi: 10.3390/jpm2010001 pmid: 25562699
2. Bartel DP. MicroRNAs. Cell. 2004;116(2):281-97. doi:
10.1016/s0092-8674(04)00045-5
3. Chiang Y, Song Y, Wang Z, Chen Y, Yue Z, Xu H, et al.
Aberrant expression of miR-203 and its clinical significance in
gastric and colorectal cancers. J Gastrointest Surg.
2011;15(1):63-70. doi: 10.1007/s11605-010-1367-8 pmid:
21063914
4. Calin GA, Croce CM. MicroRNA signatures in human cancers.
Nat Rev Cancer. 2006;6(11):857-66. doi: 10.1038/nrc1997
pmid: 17060945
5. Liang YJ, Wang QY, Zhou CX, Yin QQ, He M, Yu XT, et al.
MiR-124 targets Slug to regulate epithelial-mesenchymal
transition and metastasis of breast cancer. Carcinogenesis.
2013;34(3):713-22. doi: 10.1093/carcin/bgs383 pmid:
23250910
6. Krol J, Loedige I, Filipowicz W. The widespread regulation of
microRNA biogenesis, function and decay. Nat Rev Genet.
2010;11(9):597-610. doi: 10.1038/nrg2843 pmid: 20661255
7. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi
S, et al. Relation between microRNA expression and
progression and prognosis of gastric cancer: a microRNA
expression analysis. Lancet Oncol. 2010;11(2):136-46. doi:
10.1016/S1470-2045(09)70343-2 pmid: 20022810
8. Zhang L, Huang J, Yang N, Greshock J, Megraw MS,
Giannakakis A, et al. microRNAs exhibit high frequency
genomic alterations in human cancer. Proc Natl Acad Sci U S
A. 2006;103(24):9136-41. doi: 10.1073/pnas.0508889103
pmid: 16754881
9. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini
P, et al. MicroRNA signatures in human ovarian cancer. Cancer
Res. 2007;67(18):8699-707. doi: 10.1158/0008-5472.CAN-
07-1936 pmid: 17875710
10. Zaman MS, Maher DM, Khan S, Jaggi M, Chauhan SC.
Current status and implications of microRNAs in ovarian
cancer diagnosis and therapy. J Ovarian Res. 2012;5(1):44.
doi: 10.1186/1757-2215-5-44 pmid: 23237306
11. Mezzanzanica D, Bagnoli M, De Cecco L, Valeri B, Canevari S.
Role of microRNAs in ovarian cancer pathogenesis and
potential clinical implications. Int J Biochem Cell Biol.
2010;42(8):1262-72. doi: 10.1016/j.biocel.2009.12.017
pmid: 20035894
12. Kunej T, Godnic I, Ferdin J, Horvat S, Dovc P, Calin GA.
Epigenetic regulation of microRNAs in cancer: an integrated
review of literature. Mutat Res. 2011;717(1-2):77-84. doi:
10.1016/j.mrfmmm.2011.03.008 pmid: 21420983
13. Han ZB, Yang Z, Chi Y, Zhang L, Wang Y, Ji Y, et al.
MicroRNA-124 suppresses breast cancer cell growth and
motility by targeting CD151. Cell Physiol Biochem.
2013;31(6):823-32. doi: 10.1159/000350100 pmid:
23816858
14. Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al.
MicroRNA-148a suppresses tumor cell invasion and
metastasis by downregulating ROCK1 in gastric cancer. Clin
Cancer Res. 2011;17(24):7574-83. doi: 10.1158/1078-
0432.CCR-11-1714 pmid: 21994419
15. Song YX, Yue ZY, Wang ZN, Xu YY, Luo Y, Xu HM, et al.
MicroRNA-148b is frequently down-regulated in gastric
cancer and acts as a tumor suppressor by inhibiting cell
proliferation. Mol Cancer. 2011;10:1. doi: 10.1186/1476-
4598-10-1 pmid: 21205300
16. Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G,
Giglio S, et al. A microRNA signature defines chemoresistance
in ovarian cancer through modulation of angiogenesis. Proc
Natl Acad Sci U S A. 2013;110(24):9845-50. doi:
10.1073/pnas.1305472110 pmid: 23697367
17. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-
coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013;12(11):847-65. doi: 10.1038/nrd4140
pmid: 24172333
18. Xia J, Wu Z, Yu C, He W, Zheng H, He Y, et al. miR-124
inhibits cell proliferation in gastric cancer through down-
regulation of SPHK1. J Pathol. 2012;227(4):470-80. doi:
10.1002/path.4030 pmid: 22450659
19. Zhang H, Wang Q, Zhao Q, Di W. MiR-124 inhibits the
migration and invasion of ovarian cancer cells by targeting
SphK1. J Ovarian Res. 2013;6(1):84. doi: 10.1186/1757-
2215-6-84 pmid: 24279510
20. Wilting SM, van Boerdonk RA, Henken FE, Meijer CJ,
Diosdado B, Meijer GA, et al. Methylation-mediated silencing
and tumour suppressive function of hsa-miR-124 in cervical
cancer. Mol Cancer. 2010;9:167. doi: 10.1186/1476-4598-9-
167 pmid: 20579385
21. Dong LL, Chen LM, Wang WM, Zhang LM. Decreased
expression of microRNA-124 is an independent unfavorable
prognostic factor for patients with breast cancer. Diagn Pathol.
2015;10:45. doi: 10.1186/s13000-015-0257-5 pmid:
25924779
22. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin
dependent kinase 6 by microRNA 124 in medulloblastoma. J
Neurooncol. 2008;90(1):1-7. doi: 10.1007/s11060-008-9624-
3 pmid: 18607543.
)