Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Yuan,Wang  Xin; Gui,Yang  Xi; Na,Wang  Na; Chao,Jiang; Yang,Xigui

doi:10.3892/ol.2015.3866

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Authors:
- Wang Xin Yuan
- Yang Xi Gui
- Wang Na Na
- Jiang Chao
- Xigui Yang
View Affiliations

Affiliations: Department of Medical Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China, Department of Medical Oncology, Yucheng People's Hospital, Yucheng, Shandong 253000, P.R. China
Published online on: November 5, 2015 https://doi.org/10.3892/ol.2015.3866
Pages: 423-432

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

Numerous studies have reported the aberrant expression profiles of microRNAs (miRNAs) in diffuse large B-cell lymphoma (DLBCL), although very few of these studies were concerned with chemoresistance to R‑CHOP in DLBCL patients. This study was designed to assess the correlation between circulating miRNA expression and chemoresistance and prognosis in DLBCL patients. At the start of the study, we demonstrated that miRNA expression levels in serum were significantly associated with those in formalin‑fixed, paraffin‑embedded tissues, which indicated that circulating miRNAs may be powerful, non‑invasive biomarkers reflecting miRNAs levels isolated from tumor tissue. Then from eight potential drug‑resistant miRNAs which were deregulated in DLBCL and which had been reported to be associated with drug resistance in other carcinomas, we screened out the circulating miR‑125b and miR‑130a, which may related to R‑CHOP resistance. Dynamic monitoring of the levels of circulating miR‑125b and miR‑130a further demonstrated that they were involved in recurrence, progression and chemoresistance in DLBCL patients. Finally, we demonstrated that high miR‑125b indicated poor prognosis, as patients with higher miR‑125b levels had a shorter overall survival. To our knowledge, this is the first study demonstrating that miR‑125b and miR‑130a are associated with the risk of chemoresistance in DLBCL patients, and that dynamic monitoring of the levels of circulating miR-125b and miR-130a predicts the therapeutic response and disease status of DLBCL patients.

View Figures

View References

1	De Paepe P and De Wolf-Peeters C: Diffuse large B cell lymphoma: a heterogeneous group of non-Hodgkin lymphomas comprising several distinct clinicopathological entities. Leukemia. 21:37–43. 2007. View Article : Google Scholar : PubMed/NCBI
2	Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, et al: Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the groupe d'Etudes des lymphomes de l'adulte. Blood. 116:2040–2045. 2010. View Article : Google Scholar : PubMed/NCBI
3	Chen CF, He X, Arslan AD, Mo YY, Reinhold WC, Pommier Y and Beck WT: Novel regulation of nuclear factor-YB by miR-485-3p affects the expression of DNA topoisomerase IIα and drug responsiveness. Mol Pharmacol. 79:735–741. 2011. View Article : Google Scholar : PubMed/NCBI
4	Kurokawa K, Tanahashi T, Iima T, Yamamoto Y, Akaike Y, Nishida K, Masuda K, Kuwano Y, Murakami Y, Fukushima M and Rokutan K: Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells. J Gastroenterol. 47:883–895. 2012. View Article : Google Scholar : PubMed/NCBI
5	Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, et al: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med. 18:74–82. 2011.PubMed/NCBI
6	Yang Y, Wu J, Guan H, Cai J, Fang L, Li J and Li M: MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2. FEBS Lett. 586:3608–3612. 2012. View Article : Google Scholar : PubMed/NCBI
7	Zhu W, Xu H, Zhu D, Zhi H, Wang T, Wang J, Jiang B, Shu Y and Liu P: miR-200bc/429 cluster modulates multidrug resistance of human cancer cell lines by targeting BCL2 and XIAP. Cancer Chemother Pharmacol. 69:723–731. 2012. View Article : Google Scholar : PubMed/NCBI
8	Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR and Mott JL: miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology. 55:465–475. 2012. View Article : Google Scholar : PubMed/NCBI
9	Borel F, Han R, Visser A, Petry H, van Deventer SJ, Jansen PL and Konstantinova P: Réseau Centre de Ressources Biologiques Foie (French Liver Biobanks Network), France: Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology. 55:821–832. 2012. View Article : Google Scholar : PubMed/NCBI
10	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
11	Pan X, Wang R and Wang ZX: The potential role of miR-451 in cancer diagnosis, prognosis and therapy. Mol Cancer Ther. 12:1153–1162. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tagawa H, Ikeda S and Sawada K: Role of microRNA in the pathogenesis of malignant lymphoma. Cancer Sci. 104:801–809. 2013. View Article : Google Scholar : PubMed/NCBI
13	Fan Y, Song X, Du H, Luo C, Wang X, Yang X, Wang Y and Wu X: Down-regulation of miR-29c in human bladder cancer and the inhibition of proliferation in T24 cell via PI3K-AKT pathway. Med Oncol. 31:652014. View Article : Google Scholar : PubMed/NCBI
14	Cittelly DM, Dimitrova I, Howe EN, Cochrane DR, Jean A, Spoelstra NS, Post MD, Lu X, Broaddus RR, Spillman MA and Richer JK: Restoration of miR-200c to ovarian cancer reduces tumor burden and increases sensitivity to paclitaxel. Mol Cancer Ther. 11:2556–2565. 2012. View Article : Google Scholar : PubMed/NCBI
15	Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, et al: Revised response criteria for malignant lymphoma. J Clin Oncol. 25:579–586. 2007. View Article : Google Scholar : PubMed/NCBI
16	Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z and Luo H: Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 7:e342102012. View Article : Google Scholar : PubMed/NCBI
17	Bitarte N, Bandres E, Boni V, Zarate R, Rodriguez J, Gonzalez-Huarriz M, Lopez I, Javier Sola J, Alonso MM, Fortes P and Garcia-Foncillas J: MicroRNA-451 is involved in the self-renewal, tumorigenicity and chemoresistance of colorectal cancer stem cells. Stem Cells. 29:1661–1671. 2011. View Article : Google Scholar : PubMed/NCBI
18	Zhang JX, Qian D, Wang FW, Liao DZ, Wei JH, Tong ZT, Fu J, Huang XX, Liao YJ, Deng HX, et al: MicroRNA-29c enhances the sensitivities of human nasopharyngeal carcinoma to cisplatin-based chemotherapy and radiotherapy. Cancer Lett. 329:91–98. 2013. View Article : Google Scholar : PubMed/NCBI
19	Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M and Doki Y: Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the AKT signaling pathway. Clin Cancer Res. 17:3029–3038. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kopp F, Oak PS, Wagner E and Roidl A: miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression. PLoS One. 7:e504692012. View Article : Google Scholar : PubMed/NCBI
21	Liu S, Tetzlaff MT, Cui R and Xu X: miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol. 181:1823–1835. 2012. View Article : Google Scholar : PubMed/NCBI
22	Kong W, He L, Coppola M, Guo J, Esposito NN, Coppola D and Cheng JQ: MicroRNA-155 regulates cell survival, growth and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem. 285:17869–17879. 2010. View Article : Google Scholar : PubMed/NCBI
23	Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, Chang YL, Huang PI, Chen YW, Shih YH, et al: Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials. 33:1462–1476. 2012. View Article : Google Scholar : PubMed/NCBI
24	Ren Y, Kang CS, Yuan XB, Zhou X, Xu P, Han L, Wang GX, Jia Z, Zhong Y, Yu S, et al: Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed. 21:303–314. 2010. View Article : Google Scholar : PubMed/NCBI
25	Bai H, Wei J, Deng C, Yang X, Wang C and Xu R: MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen. Int J Hematol. 97:223–231. 2013. View Article : Google Scholar : PubMed/NCBI
26	Zhang X, Huang L, Zhao Y and Tan W: Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly. Acta Biochim Biophys Sin (Shanghai). 45:995–1001. 2013. View Article : Google Scholar : PubMed/NCBI
27	Zhou YM, Liu J and Sun W: MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac J Cancer Prev. 15:1391–1396. 2014. View Article : Google Scholar : PubMed/NCBI
28	Yang L, Li N, Wang H, Jia X, Wang X and Luo J: Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance. Oncol Rep. 28:592–600. 2012.PubMed/NCBI
29	Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q and Zhang J: Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell. Biochem Biophys Res Commun. 425:468–472. 2012. View Article : Google Scholar : PubMed/NCBI
30	Kosaka N, Iguchi H and Ochiya T: Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 101:2087–2092. 2010. View Article : Google Scholar : PubMed/NCBI
31	LaConti JJ, Shivapurkar N, Preet A, Deslattes Mays A, Peran I, Kim SE, Marshall JL, Riegel AT and Wellstein A: Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer. PLoS One. 6:e206872011. View Article : Google Scholar : PubMed/NCBI
32	Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC and Ellinger J: Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 77:1265.e9–e16. 2011. View Article : Google Scholar
33	Li HY, Zhang Y, Cai JH and Bian HL: MicroRNA-451 inhibits growth of human colorectal carcinoma cells via down-regulation of Pi3k/Akt pathway. Asian Pac J Cancer Prev. 14:3631–3634. 2013. View Article : Google Scholar : PubMed/NCBI
34	Chen H, Untiveros GM, McKee LA, Perez J, Li J, Antin PB and Konhilas JP: Micro-RNA-195 and −451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One. 7:e415742012. View Article : Google Scholar : PubMed/NCBI
35	He L, Wang HY, Zhang L, Huang L, Li JD, Xiong Y, Zhang MY, Jia WH, Yun JP, Luo RZ and Zheng M: Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer. Cell Death Dis. 5:e12052014. View Article : Google Scholar : PubMed/NCBI
36	Li B, Huang P, Qiu J, Liao Y, Hong J and Yuan Y: MicroRNA-130a is down-regulated in hepatocellular carcinoma and associates with poor prognosis. Med Oncol. 31:2302014. View Article : Google Scholar : PubMed/NCBI
37	Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D and Aguiar RC: MicroRNAs miR-125a and miR-125b constitutively activate the NF-κB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci USA. 109:7865–7870. 2012. View Article : Google Scholar : PubMed/NCBI
38	Davoudi Z, Akbarzadeh A, Rahmatiyamchi M, Movassaghpour AA, Alipour M, Nejati-Koshki K, Sadeghi Z, Dariushnejad H and Zarghami N: Molecular target therapy of AKT and NF-kB signaling pathways and multidrug resistance by specific cell penetrating inhibitor peptides in HL-60 cells. Asian Pac J Cancer Prev. 15:4353–4358. 2014. View Article : Google Scholar : PubMed/NCBI
39	Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A, et al: Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 459:717–721. 2009. View Article : Google Scholar : PubMed/NCBI
40	Chen J, Wang W, Zhang Y, Chen Y and Hu T: Predicting distant metastasis and chemoresistance using plasma miRNAs. Med Oncol. 31:7992014. View Article : Google Scholar : PubMed/NCBI
41	Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, et al: The revised international prognostic index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 109:1857–1861. 2007. View Article : Google Scholar : PubMed/NCBI