Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2015

Open Access 01-12-2015 | Research

MiRNA-149 modulates chemosensitivity of ovarian cancer A2780 cells to paclitaxel by targeting MyD88

Authors: Yueping Zhan, Fenfen Xiang, Rong Wu, Jian Xu, Zhenhua Ni, Jiemin Jiang, Xiangdong Kang

Published in: Journal of Ovarian Research | Issue 1/2015

Login to get access

Abstract

Background

The low effectiveness of anticancer drugs remains a major unresolved obstacle to successful chemotherapy. Recently, much evidence on the roles of miRNAs in determining drug-sensitivity/resistance has been emerging. The relationship between miRNA-149 expression and paclitaxel chemoresistance in human ovarian cancer cells remains largely unknown.

Methods

This study investigated the relationship between miRNA-149 expression and the sensitivity of ovarian cancer A2780 cells to paclitaxel treatment. To achieve the down-regulation of miRNA-149 gene expression in A2780 cell line, the cells were infected with lentivirus carrying inhibitor of miRNA-149. Western blot and qRT-PCR were used to detect relevant protein levels and the expressions of mRNAs of interest. Cell proliferation was measured by CCK-8 assay. Flow cytometry was used to measure cell cycle and apoptosis. Transwell migration assay was used to observe the change of migration of transfected cells.

Results

Down-regulation of miRNA-149 decreased the sensitivity of ovarian cancer A2780 cells to paclitaxel. After paclitaxel treatment, decreased apoptosis and G2 phase ratio, increased cell migration, increased level of Bcl-2, and decreased level of Bax were found in miRNA-149-down-regulated A2780 cells. MiRNA-149 down-regulation resulted in increased expression of MyD88 in A2780 cells. Down-regulation of miRNA-149 in A2780 cells increased MyD88 expression and decreased their sensitivity to paclitaxel treatment.

Conclusion

Our findings suggest that miRNA-149 mediates the susceptibility of paclitaxel by regulating MyD88 expression in ovarian cancer cells.
Literature
1.
2.
3.
Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, et al. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res. 2005;11(1):298–305.PubMed
4.
Filippetti F, Martinelli E, Ferrandina G, Gallo D, Ranelletti FO, Scambia G, et al. Bcl-2 down-Regulation is a novel mechanism of paclitaxel resistance. Mol Pharmacol. 2003;64:51–8.PubMedCrossRef
5.
Liu Z, Zhu G, Getzenberg RH, Veltri RW. The upregulation of PI3K/Akt and MAP kinase pathways is associated with resistance of microtubule-targeting drugs in prostate cancer. J Cell Biochem. 2015. doi:10.​1002/​jcb.​25091.PubMedCentral
6.
7.
8.
Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010;11:252–63.PubMedCrossRef
9.
Cui Q, Yu Z, Purisima EO, Wang E. Microrna regulation and interspecific variation of gene expression. Trends Genet. 2007;23(8):372–5.PubMedCrossRef
10.
Xu G, Zhang Z, Xing Y, Wei J, Ge Z, Liu X, et al. Microrna-149 negatively regulates tlr-triggered inflammatory response in macrophages by targeting myd88. J Cell Biochem. 2014;115(5):919–27.PubMedCrossRef
11.
Xiang F, Wu R, Ni Z, Pan C, Zhan Y, Xu J, et al. MyD88 expression is associated with paclitaxel resistance in lung cancer A549 cells. Oncol Rep. 2014;32(5):1837–44.PubMed
12.
Ishihara T, Seki N, Inoguchi S, Yoshino H, Tatarano S, Yamada Y, et al. Expression of the tumor suppressive mirna-23b/27b cluster is a good prognostic marker in clear cell renal cell carcinoma. J Urol. 2014;192(6):1822–30.PubMedCrossRef
13.
Ma MT, He M, Wang Y, Jiao XY, Zhao L, Bai XF, et al. Mir-487a resensitizes mitoxantrone (mx)-resistant breast cancer cells (mcf-7/mx) to mx by targeting breast cancer resistance protein (bcrp/abcg2). Cancer Lett. 2013;339(1):107–15.PubMedCrossRef
14.
To KK, Zhan Z, Litman T, Bates SE. Regulation of abcg2 expression at the 3' untranslated region of its mrna through modulation of transcript stability and protein translation by a putative microrna in the s1 colon cancer cell line. Mol Cell Biol. 2008;28(17):5147–61.PubMedCentralPubMedCrossRef
15.
Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C. Role of micrornas in drug-resistant ovarian cancer cells. Gynecol Oncol. 2008;111(3):478–86.PubMedCrossRef
16.
Chan JK, Blansit K, Kiet T, Sherman A, Wong G, Earle C, et al. The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer. Gynecol Oncol. 2014;132(3):739–44.PubMedCrossRef
17.
Chen XP, Chen YG, Lan JY, Shen ZJ. MicroRNA-370 suppresses proliferation and promotes endometrioid ovarian cancer chemosensitivity to cDDP by negatively regulating ENG. Cancer Lett. 2014;353(2):201–10.PubMedCrossRef
18.
Fu X, Tian J, Zhang L, Chen Y, Hao Q. Involvement of microrna-93, a new regulator of pten/akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett. 2012;586(9):1279–86.PubMedCrossRef
19.
Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44.PubMedCentralPubMed
20.
Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of micrornas in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut. 2009;58(10):1375–81.PubMedCrossRef
21.
Luo Z, Zhang L, Li Z, Li X, Li G, Yu H, et al. An in silico analysis of dynamic changes in microrna expression profiles in stepwise development of nasopharyngeal carcinoma. BMC Med Genomics. 2012;5:3.PubMedCentralPubMedCrossRef
22.
Liu H, Brannon AR, Reddy AR, Alexe G, Seiler MW, Arreola A, et al. Identifying mrna targets of microrna dysregulated in cancer: With application to clear cell renal cell carcinoma. BMC Syst Biol. 2010;4:51.PubMedCentralPubMedCrossRef
23.
Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126(5):1166–76.PubMed
24.
Wang Y, Zheng X, Zhang Z, Zhou J, Zhao G, Yang J, et al. Microrna-149 inhibits proliferation and cell cycle progression through the targeting of zbtb2 in human gastric cancer. PLoS One. 2012;7(10):e41693.PubMedCentralPubMedCrossRef
25.
Li D, Chen P, Li XY, Zhang LY, Xiong W, Zhou M, et al. Grade-specific expression profiles of mirnas/mrnas and docking study in human grade i-iii astrocytomas. OMICS. 2011;15(10):673–82.PubMedCrossRef
26.
Wang F, Ma YL, Zhang P, Shen TY, Shi CZ, Yang YZ, et al. Sp1 mediates the link between methylation of the tumour suppressor mir-149 and outcome in colorectal cancer. J Pathol. 2013;229(1):12–24.PubMedCrossRef
27.
Wang EL, Qian ZR, Nakasono M, Tanahashi T, Yoshimoto K, Bando Y, et al. High expression of toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J Cancer. 2010;102(5):908–15.PubMedCentralPubMedCrossRef
28.
Xiang WQ, Feng WF, Ke W, Sun Z, Chen Z, Liu W. Hepatitis b virus x protein stimulates il-6 expression in hepatocytes via a myd88-dependent pathway. J Hepatol. 2011;54(1):26–33.PubMedCrossRef
29.
Szajnik M, Szczepanski MJ, Czystowska M, Elishaev E, Mandapathil M, Nowak-Markwitz E, et al. Tlr4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer. Oncogene. 2009;28(49):4353–63.PubMedCentralPubMedCrossRef
30.
Zhou M, McFarland-Mancini MM, Funk HM, Husseinzadeh N, Mounajjed T, Drew AF. Toll-like receptor expression in normal ovary and ovarian tumors. Cancer Immunol Immunother. 2009;58(9):1375–85.PubMedCrossRef
31.
Wang AC, Su QB, Wu FX, Zhang XL, Liu PS. Role of tlr4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells. Eur J Clin Invest. 2009;39(2):157–64.PubMedCrossRef
32.
Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, et al. Tlr-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66(7):3859–68.PubMedCrossRef
33.
Liang B, Chen R, Wang T, Cao L, Liu Y, Yin F, et al. Myeloid differentiation factor 88 promotes growth and metastasis of human hepatocellular carcinoma. Clin Cancer Res. 2013;19(11):2905–16.PubMedCrossRef
34.
Holleman A, Chung I, Olsen RR, Kwak B, Mizokami A, Saijo N, et al. Mir-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene. 2011;30(43):4386–98.PubMedCentralPubMedCrossRef
35.
Shi J, Orth JD, Mitchison T. Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res. 2008;68(9):3269–76.PubMedCrossRef
36.
Haldar S, Chintapalli J, Croce CM. Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res. 1996;56(6):1253–5.PubMed
37.
Perkins C, Kim CN, Fang G, Bhalla KN. Overexpression of Apaf-1 promotes apoptosis of untreated and paclitaxel- or etoposide-treated HL-60 cells. Cancer Res. 1998;58(20):4561–6.PubMed
38.
Goncalves A, Braguer D, Carles G, Andre N, Prevot C, Briand C. Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer cells (HT29-D4). Biochem Pharmacol. 2000;60(11):1579–84.PubMedCrossRef
39.
Chan SH, Huang WC, Chang JW, Chang KJ, Kuo WH, Wang MY, et al. Microrna-149 targets git1 to suppress integrin signaling and breast cancer metastasis. Oncogene. 2014;33(36):4496–507.PubMedCentralPubMedCrossRef
Metadata
Title
MiRNA-149 modulates chemosensitivity of ovarian cancer A2780 cells to paclitaxel by targeting MyD88
Authors
Yueping Zhan
Fenfen Xiang
Rong Wu
Jian Xu
Zhenhua Ni
Jiemin Jiang
Xiangdong Kang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2015
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-015-0178-7

Other articles of this Issue 1/2015

Journal of Ovarian Research 1/2015 Go to the issue

Research

Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women

Research

Intratumoral interleukin-6 predicts ascites formation in patients with epithelial ovarian cancer: A potential tool for close monitoring

Research

Effect of targeted ovarian cancer immunotherapy using ovarian cancer stem cell vaccine

Review

VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation

Research

Differential expression of lysosome-associated protein transmembrane-4 beta (LAPTM4B) in granulosa cells of ovarian follicles and in other bovine tissues

Research

Integrative network analysis for survival-associated gene-gene interactions across multiple genomic profiles in ovarian cancer