Top

Published in:

01-07-2016 | Original Article

miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma

Authors: Shuguang Zhou, Bing Wang, Jun Hu, Yucheng Zhou, Mengzhen Jiang, Mingyu Wu, Liming Qin, Xuming Yang

Published in: Tumor Biology | Issue 7/2016

Abstract

MicroRNAs (miRNAs) are a new class of prognostic and diagnostic biomarkers for many cancers. Recent studies have shown that miRNAs are highly stable in plasma/serum. The aim of this study was to investigate the role of miR-421 in osteosarcoma. We found that the serum expression levels of miR-421 were significantly higher in osteosarcoma patients than those in healthy volunteers. Moreover, miR-421 expression was significantly higher in osteosarcoma tissues compared with that in the adjacent normal tissues. Meanwhile, the expression of miR-421 was upregulated in 90 % (36/40) osteosarcoma tissues compared to non-tumor tissues. More importantly, the expression levels of miR-421 in osteosarcoma tissues were correlated with those in patients’ serum. In addition, patients with high miR-421 expression had shorter overall survival (OS) than those with low expressions. We also found that overexpression of miR-421 promoted osteosarcoma cell line MG-63 proliferation, migration, and invasion. In conclusion, miR-421 expression levels were upregulated in osteosarcoma tissue and serum and it may be a useful marker for diagnosis of osteosarcoma.

Available only for authorised users

Tang J, Shen L, Yang Q, Zhang C. Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition. Cell Prolif. 2014;47(5):427–34. doi:10.1111/cpr.12129.CrossRefPubMed

Tsai HC, Su HL, Huang CY, Fong YC, Hsu CJ, Tang CH. CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d. Oncotarget. 2014;5(11):3800–12.CrossRefPubMedPubMedCentral

Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, et al. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PloS One. 2013;8(1):e53906. doi:10.1371/journal.pone.0053906.CrossRefPubMedPubMedCentral

Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, et al. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PloS One. 2012;7(3):e33778. doi:10.1371/journal.pone.0033778.CrossRefPubMedPubMedCentral

Namlos HM, Meza-Zepeda LA, Baroy T, Ostensen IH, Kresse SH, Kuijjer ML, et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PloS One. 2012;7(10):e48086. doi:10.1371/journal.pone.0048086.CrossRefPubMedPubMedCentral

Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, et al. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72(7):1865–77. doi:10.1158/0008-5472.CAN-11-2663.CrossRefPubMedPubMedCentral

Mei Q, Li F, Quan H, Liu Y, Xu H. Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo. Cancer Sci. 2014;105(7):755–62. doi:10.1111/cas.12436.CrossRefPubMedPubMedCentral

Li Y, Zhang J, Zhang L, Si M, Yin H, Li J. Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of osteosarcoma cells by switching on suppressor microRNAs and inactivating of Notch-1 signaling. Carcinogenesis. 2013;34(7):1601–10. doi:10.1093/carcin/bgt065.CrossRefPubMed

Pan Z, Sun X, Shan H, Wang N, Wang J, Ren J, et al. MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-beta1 pathway. Circulation. 2012;126(7):840–50. doi:10.1161/CIRCULATIONAHA.112.094524.CrossRefPubMed

10.

Martinez-Pacheco M, Hidalgo-Miranda A, Romero-Cordoba S, Valverde M, Rojas E. MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects. Gene. 2014;533(2):508–14. doi:10.1016/j.gene.2013.09.049.CrossRefPubMed

11.

Li S, Fu H, Wang Y, Tie Y, Xing R, Zhu J, et al. MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatol. 2009;49(4):1194–202. doi:10.1002/hep.22757.CrossRef

12.

Yu L, Ding GF, He C, Sun L, Jiang Y, Zhu L. MicroRNA-424 is down-regulated in hepatocellular carcinoma and suppresses cell migration and invasion through c-Myb. PloS One. 2014;9(3):e91661. doi:10.1371/journal.pone.0091661.CrossRefPubMedPubMedCentral

13.

Li Z, Yu X, Shen J, Chan MT, Wu WK. MicroRNA in intervertebral disc degeneration. Cell Prolif. 2015. doi: 10.1111/cpr.12180.

14.

Li Z, Yu X, Shen J, Wu WK, Chan MT. MicroRNA expression and its clinical implications in Ewing’s sarcoma. Cell Prolif. 2015;48(1):1–6. doi:10.1111/cpr.12160.CrossRefPubMed

15.

Yu X, Li Z, Liu J. MiRNAs in primary cutaneous lymphomas. Cell Prolif. 2015. doi: 10.1111/cpr.12179.

16.

Yu X, Li Z, Shen J, Wu WK, Liang J, Weng X, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt Pathway by Targeting HOXD10 in intervetebral Disc Degeneration. PloS One. 2013;8(12):e83080. doi:10.1371/journal.pone.0083080.CrossRefPubMedPubMedCentral

17.

Ohdaira H, Sekiguchi M, Miyata K, Yoshida K. MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif. 2012;45(1):32–8. doi:10.1111/j.1365-2184.2011.00798.x.CrossRefPubMed

18.

Li M, Yu M, Liu C, Zhu H, He X, Peng S, et al. miR-34c works downstream of p53 leading to dairy goat male germline stem-cell (mGSCs) apoptosis. Cell Prolif. 2013;46(2):223–31. doi:10.1111/cpr.12013.CrossRefPubMed

19.

Fu LL, Zhao X, Xu HL, Wen X, Wang SY, Liu B, et al. Identification of microRNA-regulated autophagic pathways in plant lectin-induced cancer cell death. Cell Prolif. 2012;45(5):477–85. doi:10.1111/j.1365-2184.2012.00840.x.CrossRefPubMed

20.

Luo X, Dong Z, Chen Y, Yang L, Lai D. Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated AKT pathway. Cell Prolif. 2013;46(4):436–46. doi:10.1111/cpr.12038.CrossRefPubMed

21.

Zhang WH, Gui JH, Wang CZ, Chang Q, Xu SP, Cai CH, et al. The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma. Oncol Res. 2012;20(4):139–47.CrossRefPubMed

22.

Liang J, Zhang Y, Jiang G, Liu Z, Xiang W, Chen X, et al. MiR-138 induces renal carcinoma cell senescence by targeting EZH2 and is downregulated in human clear cell renal cell carcinoma. Oncol Res. 2013;21(2):83–91. doi:10.3727/096504013X13775486749218.CrossRefPubMed

23.

Zhou J, Song S, Cen J, Zhu D, Li D, Zhang Z. MicroRNA-375 is downregulated in pancreatic cancer and inhibits cell proliferation in vitro. Oncol Res. 2012;20(5-6):197–203.CrossRefPubMed

24.

Xiao X, Tang C, Xiao S, Fu C, Yu P. Enhancement of proliferation and invasion by MicroRNA-590-5p via targeting PBRM1 in clear cell renal carcinoma cells. Oncol Res. 2013;20(11):537–44. doi:10.3727/096504013X13775486749335.CrossRefPubMed

25.

Kulkarni S, Augoff K, Rivera L, McCue B, Khoury T, Groman A, et al. Increased expression levels of WAVE3 are associated with the progression and metastasis of triple negative breast cancer. PloS One. 2012;7(8):e42895. doi:10.1371/journal.pone.0042895.CrossRefPubMedPubMedCentral

26.

Creighton CJ, Hernandez-Herrera A, Jacobsen A, Levine DA, Mankoo P, Schultz N, et al. Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma. PloS One. 2012;7(3):e34546. doi:10.1371/journal.pone.0034546.CrossRefPubMedPubMedCentral

27.

Ma R, Yan W, Zhang G, Lv H, Liu Z, Fang F, et al. Upregulation of miR-196b confers a poor prognosis in glioblastoma patients via inducing a proliferative phenotype. PloS One. 2012;7(6):e38096. doi:10.1371/journal.pone.0038096.CrossRefPubMedPubMedCentral

28.

Gong M, Ma J, Guillemette R, Zhou M, Yang Y, Hock JM, et al. MiR-335 inhibits small cell lung cancer bone metastases via IGF-IR and RANKL pathways. Mol Cancer Res. 2014;12(1):101–10. doi:10.1158/1541-7786.MCR-13-0136.CrossRefPubMed

29.

Geekiyanage H, Jicha GA, Nelson PT, Chan C. Blood serum miRNA: non-invasive biomarkers for Alzheimer’s disease. Exp Neurol. 2012;235(2):491–6. doi:10.1016/j.expneurol.2011.11.026.CrossRefPubMed

30.

Wang M, Gu H, Wang S, Qian H, Zhu W, Zhang L, et al. Circulating miR-17-5p and miR-20a: molecular markers for gastric cancer. Mol Med Report. 2012;5(6):1514–20. doi:10.3892/mmr.2012.828.

31.

Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, et al. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2013;105(12):849–59. doi:10.1093/jnci/djt101.CrossRefPubMedPubMedCentral

32.

Gao Y, Luo LH, Li S, Yang C. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun. 2014;444(2):230–4. doi:10.1016/j.bbrc.2014.01.061.CrossRefPubMed

33.

Lei P, Xie J, Wang L, Yang X, Dai Z, Hu Y. microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1. Mol Med Rep. 2014;10(1):155–60. doi:10.3892/mmr.2014.2195.PubMed

34.

Huang YZ, Zhang J, Shao HY, Chen JP, Zhao HY. MicroRNA-191 promotes osteosarcoma cells proliferation by targeting checkpoint kinase 2. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2015. doi: 10.1007/s13277-015-3290-9.

35.

Zhang Y, Duan G, Feng S. MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Biochem Biophys Res Commun. 2015;459(3):367–73. doi:10.1016/j.bbrc.2015.02.101.CrossRefPubMed

36.

Chen L, Tang Y, Wang J, Yan Z, Xu R. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4. Biochem Biophys Res Commun. 2013;435(4):745–50. doi:10.1016/j.bbrc.2013.05.056.CrossRefPubMed

37.

Wu JH, Yao YL, Gu T, Wang ZY, Pu XY, Sun WW, et al. MiR-421 regulates apoptosis of BGC-823 gastric cancer cells by targeting caspase-3. Asian Pac J Cancer Prev. 2014;15(13):5463–8.CrossRefPubMed

38.

Jiang Z, Guo J, Xiao B, Miao Y, Huang R, Li D, et al. Increased expression of miR-421 in human gastric carcinoma and its clinical association. J Gastroenterol. 2010;45(1):17–23. doi:10.1007/s00535-009-0135-6.CrossRefPubMed

39.

Hao J, Zhang S, Zhou Y, Liu C, Hu X, Shao C. MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer. Biochem Biophys Res Commun. 2011;406(4):552–7. doi:10.1016/j.bbrc.2011.02.086.CrossRefPubMed

40.

Wu J, Li G, Yao Y, Wang Z, Sun W, Wang J. MicroRNA-421 is a new potential diagnosis biomarker with higher sensitivity and specificity than carcinoembryonic antigen and cancer antigen 125 in gastric cancer. Biomarker. 2015;20(1):58–63. doi:10.3109/1354750X.2014.992812.CrossRef

41.

Cai H, Zhao H, Tang J, Wu H. Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J Surg Res. 2015;194(2):505–10. doi:10.1016/j.jss.2014.11.025.CrossRefPubMed

42.

Zhang C, Yao C, Li H, Wang G, He X. Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in patients with osteosarcoma. Int J Clin Exp Pathol. 2014;7(7):4194–203.PubMedPubMedCentral

43.

Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, Lakomy R, et al. Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. Journal of translational medicine. 2012;10:55. doi:10.1186/1479-5876-10-55.CrossRefPubMedPubMedCentral

44.

Zhou L, Zhao YP, Liu WJ, Dong J, Chen WY, Zhang TP, et al. Circulating microRNAs in cancer: diagnostic and prognostic significance. Expert Rev Anticancer Ther. 2012;12(2):283–8. doi:10.1586/era.11.197.CrossRefPubMed

45.

Hong Q, Fang J, Pang Y, Zheng J. Prognostic value of the microRNA-29 family in patients with primary osteosarcomas. Med Oncol. 2014;31(8):37. doi:10.1007/s12032-014-0037-1.CrossRefPubMed

46.

Yuan J, Chen L, Chen X, Sun W, Zhou X. Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma. J Int Med Res. 2012;40(6):2090–7.CrossRefPubMed

47.

Wang RJ, Zheng YH, Wang P, Zhang JZ. Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8(1):765–71.PubMedPubMedCentral

48.

Zhao FL, Hu GD, Wang XF, Zhang XH, Zhang YK, Yu ZS. Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res. 2012;40(3):859–66.CrossRefPubMed

49.

Faltejskova P, Bocanek O, Sachlova M, Svoboda M, Kiss I, Vyzula R, et al. Circulating miR-17-3p, miR-29a, miR-92a and miR-135b in serum: evidence against their usage as biomarkers in colorectal cancer. Cancer Biomark. 2012;12(4):199–204. doi:10.3233/CBM-130308.PubMed

Title: miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma
Authors: Shuguang Zhou
Bing Wang
Jun Hu
Yucheng Zhou
Mengzhen Jiang
Mingyu Wu
Liming Qin
Xuming Yang
Publication date: 01-07-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4578-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2016

SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer

Combination of platelet count and mean platelet volume (COP-MPV) predicts postoperative prognosis in both resectable early and advanced stage esophageal squamous cell cancer patients

Hypersplenism is correlated with increased risk of hepatocellular carcinoma in patients with post-hepatitis cirrhosis

Critical role for the long non-coding RNA AFAP1-AS1 in the proliferation and metastasis of hepatocellular carcinoma

Expression and prognostic value of miR-92a in patients with gastric cancer

Long noncoding RNA H19 contributes to gallbladder cancer cell proliferation by modulated miR-194-5p targeting AKT2

Keynote webinar | Spotlight on antibody–drug conjugates in cancer