Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma

Zhou,Jun; Gong,Guanghui; Tan,Hong; Dai,Furong; Zhu,Xin; Chen,Yile; Wang,Junpu; Liu,Ying; Chen,Puxiang; Wu,Xiaoying; Wen,Jifang

doi:10.3892/or.2015.3937

Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma

Authors:
- Jun Zhou
- Guanghui Gong
- Hong Tan
- Furong Dai
- Xin Zhu
- Yile Chen
- Junpu Wang
- Ying Liu
- Puxiang Chen
- Xiaoying Wu
- Jifang Wen
View Affiliations

Affiliations: Department of Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan 410013, P.R. China, Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Gynecology Oncology, Hunan Tumor Hospital, Changsha, Hunan 410013, P.R. China, Department of Gynecology and Obstetrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: April 28, 2015 https://doi.org/10.3892/or.2015.3937
Pages: 2915-2923

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR‑30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR‑30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adenocarcinoma patients, while the inhibition of miR-30a-5p suppressed the malignant phenotypes of ovarian cancer in vitro. Therefore, miR-30a-5p serves as a promising diagnostic and therapeutic target for ovarian serous adenocarcinoma.

View Figures

View References

1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
2	Wright JD, Shah M, Mathew L, Burke WM, Culhane J, Goldman N, Schiff PB and Herzog TJ: Fertility preservation in young women with epithelial ovarian cancer. Cancer. 115:4118–4126. 2009. View Article : Google Scholar : PubMed/NCBI
3	van Nagell JR Jr and Hoff JT: Transvaginal ultrasonography in ovarian cancer screening: Current perspectives. Int J Womens Health. 6:25–33. 2013. View Article : Google Scholar :
4	Leung F, Diamandis EP and Kulasingam V: Ovarian cancer biomarkers: Current state and future implications from high-throughput technologies. Adv Clin Chem. 66:25–77. 2014. View Article : Google Scholar : PubMed/NCBI
5	Jacobs I and Bast RC Jr: The CA 125 tumour-associated antigen: A review of the literature. Hum Reprod. 4:1–12. 1989.PubMed/NCBI
6	Cohen JG, White M, Cruz A and Farias-Eisner R: In 2014, can we do better than CA125 in the early detection of ovarian cancer? World J Biol Chem. 5:286–300. 2014. View Article : Google Scholar : PubMed/NCBI
7	Berek JS and Bast RC Jr: Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection. Cancer. 76(Suppl 10): S2092–S2096. 1995. View Article : Google Scholar
8	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
9	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
10	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
13	Neal CS, Michael MZ, Pimlott LK, Yong TY, Li JY and Gleadle JM: Circulating microRNA expression is reduced in chronic kidney disease. Nephrol Dial Transplant. 26:3794–3802. 2011. View Article : Google Scholar : PubMed/NCBI
14	Lorenzen JM, Volkmann I, Fiedler J, Schmidt M, Scheffner I, Haller H, Gwinner W and Thum T: Urinary miR-210 as a mediator of acute T-cell mediated rejection in renal allograft recipients. Am J Transplant. 11:2221–2227. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, Warnecke JM and Sczakiel G: A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 28:655–661. 2010. View Article : Google Scholar
16	Wang G, Tam LS, Li EK, Kwan BC, Chow KM, Luk CC, Li PK and Szeto CC: Serum and urinary cell-free miR-146a and miR-155 in patients with systemic lupus erythematosus. J Rheumatol. 37:2516–2522. 2010. View Article : Google Scholar : PubMed/NCBI
17	Luo Y, Wang C, Chen X, Zhong T, Cai X, Chen S, Shi Y, Hu J, Guan X, Xia Z, et al: Increased serum and urinary microRNAs in children with idiopathic nephrotic syndrome. Clin Chem. 59:658–666. 2013. View Article : Google Scholar : PubMed/NCBI
18	Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, et al: MicroRNA signatures in human ovarian cancer. Cancer Res. 67:8699–8707. 2007. View Article : Google Scholar : PubMed/NCBI
19	Taylor DD and Gercel-Taylor C: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 110:13–21. 2008. View Article : Google Scholar : PubMed/NCBI
20	Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM and Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 112:55–59. 2009. View Article : Google Scholar
21	Jiang X, Du L, Wang L, Li J, Liu Y, Zheng G, Qu A, Zhang X, Pan H, Yang Y, et al: Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer. Int J Cancer. 136:854–862. 2015. View Article : Google Scholar
22	Wang K, Jia Z, Zou J, Zhang A, Wang G, Hao J, Wang Y, Yang S and Pu P: Analysis of hsa-miR-30a-5p expression in human gliomas. Pathol Oncol Res. 19:405–411. 2013. View Article : Google Scholar : PubMed/NCBI
23	Vlassov AV, Magdaleno S, Setterquist R and Conrad R: Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 1820:940–948. 2012. View Article : Google Scholar : PubMed/NCBI
24	Gu Y, Li M, Wang T, Liang Y, Zhong Z, Wang X, Zhou Q, Chen L, Lang Q, He Z, et al: Lactation-related microRNA expression profiles of porcine breast milk exosomes. PLoS One. 7:e436912012. View Article : Google Scholar : PubMed/NCBI
25	Keller S, Ridinger J, Rupp AK, Janssen JW and Altevogt P: Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med. 9:862011. View Article : Google Scholar : PubMed/NCBI
26	Xi Y, Formentini A, Chien M, Weir DB, Russo JJ and Ju J, Kornmann M and Ju J: Prognostic values of microRNAs in colorectal cancer. Biomark Insights. 2:113–121. 2006.
27	Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, et al: Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 26:7590–7595. 2007. View Article : Google Scholar : PubMed/NCBI
28	Li X, Zhang Y, Zhang Y, Ding J, Wu K and Fan D: Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 59:579–585. 2010. View Article : Google Scholar
29	Baraniskin A, Birkenkamp-Demtroder K, Maghnouj A, Zöllner H, Munding J, Klein-Scory S, Reinacher-Schick A, Schwarte-Waldhoff I, Schmiegel W and Hahn SA: MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL. Carcinogenesis. 33:732–739. 2012. View Article : Google Scholar : PubMed/NCBI
30	Jia Z, Wang K, Wang G, Zhang A and Pu P: MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7. PLoS One. 8:e550082013. View Article : Google Scholar : PubMed/NCBI