Skip to main content
Erschienen in: Medical Oncology 2/2014

01.02.2014 | Original Paper

Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma

verfasst von: Yisila Mu, Haoshaqiang Zhang, Lixin Che, Kun Li

Erschienen in: Medical Oncology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues (r = −0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02), poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease.
Literatur
1.
Zurück zum Zitat Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.PubMedCrossRef Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.PubMedCrossRef
2.
Zurück zum Zitat Gill J, Ahluwalia MK, Geller D, Gorlick R. New targets and approaches in osteosarcoma. Pharmacol Ther. 2013;137:89–99.PubMedCrossRef Gill J, Ahluwalia MK, Geller D, Gorlick R. New targets and approaches in osteosarcoma. Pharmacol Ther. 2013;137:89–99.PubMedCrossRef
3.
4.
Zurück zum Zitat Poletajew S, Fus L, Wasiutyński A. Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. Ortop Traumatol Rehabil. 2011;13:537–45.PubMedCrossRef Poletajew S, Fus L, Wasiutyński A. Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. Ortop Traumatol Rehabil. 2011;13:537–45.PubMedCrossRef
5.
Zurück zum Zitat PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.PubMedCentralPubMedCrossRef PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Chou J, Shahi P, Werb Z. MicroRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013;12:3262–71.PubMedCrossRef Chou J, Shahi P, Werb Z. MicroRNA-mediated regulation of the tumor microenvironment. Cell Cycle. 2013;12:3262–71.PubMedCrossRef
7.
Zurück zum Zitat Miao J, Wu S, Peng Z, Tania M, Zhang C. MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects. Tumour Biol. 2013;34:2093–8.PubMedCrossRef Miao J, Wu S, Peng Z, Tania M, Zhang C. MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects. Tumour Biol. 2013;34:2093–8.PubMedCrossRef
8.
Zurück zum Zitat Zhou G, Shi X, Zhang J, Wu S, Zhao J. MicroRNAs in osteosarcoma: from biological players to clinical contributors, a review. J Int Med Res. 2013;41:1–12.PubMedCrossRef Zhou G, Shi X, Zhang J, Wu S, Zhao J. MicroRNAs in osteosarcoma: from biological players to clinical contributors, a review. J Int Med Res. 2013;41:1–12.PubMedCrossRef
9.
Zurück zum Zitat Liang W, Gao B, Fu P, Xu S, Qian Y, Fu Q. The miRNAs in the pathgenesis of osteosarcoma. Front Biosci. 2013;18:788–94.CrossRef Liang W, Gao B, Fu P, Xu S, Qian Y, Fu Q. The miRNAs in the pathgenesis of osteosarcoma. Front Biosci. 2013;18:788–94.CrossRef
11.
Zurück zum Zitat Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.PubMedCentralPubMed Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.PubMedCentralPubMed
12.
Zurück zum Zitat 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;40:2090–7.PubMedCrossRef 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;40:2090–7.PubMedCrossRef
13.
Zurück zum Zitat Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58:2170–5.PubMed Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58:2170–5.PubMed
14.
Zurück zum Zitat Motoyama K, Inoue H, Takatsuno Y, et al. Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 2009;34:1069–75.PubMed Motoyama K, Inoue H, Takatsuno Y, et al. Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 2009;34:1069–75.PubMed
15.
Zurück zum Zitat Lin WM, Baker AC, Beroukhim R, et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 2008;68:664–73.PubMedCrossRef Lin WM, Baker AC, Beroukhim R, et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 2008;68:664–73.PubMedCrossRef
16.
17.
Zurück zum Zitat Ueno K, Hirata H, Shahryari V, et al. MicroRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer. Br J Cancer. 2013;108:1659–67.PubMedCrossRef Ueno K, Hirata H, Shahryari V, et al. MicroRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer. Br J Cancer. 2013;108:1659–67.PubMedCrossRef
18.
Zurück zum Zitat Tanaka H, Sasayama T, Tanaka K, et al. MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells. J Neurooncol. 2013;111:273–83.PubMedCrossRef Tanaka H, Sasayama T, Tanaka K, et al. MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells. J Neurooncol. 2013;111:273–83.PubMedCrossRef
19.
Zurück zum Zitat Wang G, Mao W, Zheng S. MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS Lett. 2008;582:3663–8.PubMedCrossRef Wang G, Mao W, Zheng S. MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS Lett. 2008;582:3663–8.PubMedCrossRef
20.
Zurück zum Zitat Zhao H, Guo M, Zhao G, et al. miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells. Int J Mol Med. 2012;30:1013–20.PubMed Zhao H, Guo M, Zhao G, et al. miR-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells. Int J Mol Med. 2012;30:1013–20.PubMed
21.
Zurück zum Zitat Zhu J, Feng Y, Ke Z, et al. Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol. 2012;180:2440–51.PubMedCrossRef Zhu J, Feng Y, Ke Z, et al. Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol. 2012;180:2440–51.PubMedCrossRef
22.
Zurück zum Zitat Shang X, Wang Y, Zhao Q, et al. siRNAs target sites selection of ezrin and the influence of RNA interference on ezrin expression and biological characters of osteosarcoma cells. Mol Cell Biochem. 2012;364:363–71.PubMedCrossRef Shang X, Wang Y, Zhao Q, et al. siRNAs target sites selection of ezrin and the influence of RNA interference on ezrin expression and biological characters of osteosarcoma cells. Mol Cell Biochem. 2012;364:363–71.PubMedCrossRef
23.
Zurück zum Zitat Li H, Min D, Zhao H, et al. The prognostic role of ezrin immunoexpression in osteosarcoma: a meta-analysis of published data. PLoS ONE. 2013;8:e64513.PubMedCentralPubMedCrossRef Li H, Min D, Zhao H, et al. The prognostic role of ezrin immunoexpression in osteosarcoma: a meta-analysis of published data. PLoS ONE. 2013;8:e64513.PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Wang Z, He ML, Zhao JM, Qing HH, Wu Y. Meta-analysis of associations of the ezrin gene with human osteosarcoma response to chemotherapy and prognosis. Asian Pac J Cancer Prev. 2013;14:2753–8.PubMedCrossRef Wang Z, He ML, Zhao JM, Qing HH, Wu Y. Meta-analysis of associations of the ezrin gene with human osteosarcoma response to chemotherapy and prognosis. Asian Pac J Cancer Prev. 2013;14:2753–8.PubMedCrossRef
25.
Zurück zum Zitat Ren L, Hong SH, Chen QR, et al. Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer Res. 2012;72:1001–12.PubMedCrossRef Ren L, Hong SH, Chen QR, et al. Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer Res. 2012;72:1001–12.PubMedCrossRef
26.
Zurück zum Zitat Bacci G, Bertoni F, Longhi A, et al. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer. 2003;97:3068–75.PubMedCrossRef Bacci G, Bertoni F, Longhi A, et al. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer. 2003;97:3068–75.PubMedCrossRef
27.
Zurück zum Zitat Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25:402–8.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25:402–8.PubMedCrossRef
28.
Zurück zum Zitat Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.PubMedCrossRef Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.PubMedCrossRef
29.
Zurück zum Zitat Jörgren F, Nilbert M, Rambech E, Bendahl PO, Lindmark G. Ezrin expression in rectal cancer predicts time to development of local recurrence. Int J Colorectal Dis. 2012;27:893–9.PubMedCrossRef Jörgren F, Nilbert M, Rambech E, Bendahl PO, Lindmark G. Ezrin expression in rectal cancer predicts time to development of local recurrence. Int J Colorectal Dis. 2012;27:893–9.PubMedCrossRef
30.
Zurück zum Zitat Arumugam P, Partelli S, Coleman SJ, et al. Ezrin expression is an independent prognostic factor in gastro-intestinal cancers. J Gastrointest Surg. 2013;17:2082–91. Arumugam P, Partelli S, Coleman SJ, et al. Ezrin expression is an independent prognostic factor in gastro-intestinal cancers. J Gastrointest Surg. 2013;17:2082–91.
31.
Zurück zum Zitat Gschwantler-Kaulich D, Natter C, Steurer S, et al. Increase in ezrin expression from benign to malignant breast tumours. Cell Oncol. 2013;36:485–91. Gschwantler-Kaulich D, Natter C, Steurer S, et al. Increase in ezrin expression from benign to malignant breast tumours. Cell Oncol. 2013;36:485–91.
32.
Zurück zum Zitat Saito S, Yamamoto H, Mukaisho K, et al. Mechanisms underlying cancer progression caused by ezrin overexpression in tongue squamous cell carcinoma. PLoS ONE. 2013;8:e54881.PubMedCentralPubMedCrossRef Saito S, Yamamoto H, Mukaisho K, et al. Mechanisms underlying cancer progression caused by ezrin overexpression in tongue squamous cell carcinoma. PLoS ONE. 2013;8:e54881.PubMedCentralPubMedCrossRef
33.
34.
Zurück zum Zitat Fadiel A, Chen Z, Ulukus E, Ohtani K, Hatami M, Naftolin F. Ezrin overexpression by transformed human ovarian surface epithelial cells, ovarian cleft cells, and serous ovarian adenocarcinoma cells. Reprod Sci. 2012;19:797–805.PubMedCrossRef Fadiel A, Chen Z, Ulukus E, Ohtani K, Hatami M, Naftolin F. Ezrin overexpression by transformed human ovarian surface epithelial cells, ovarian cleft cells, and serous ovarian adenocarcinoma cells. Reprod Sci. 2012;19:797–805.PubMedCrossRef
35.
Zurück zum Zitat Wan X, Mendoza A, Khanna C, Helman LJ. Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res. 2005;65:2406–11.PubMedCrossRef Wan X, Mendoza A, Khanna C, Helman LJ. Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res. 2005;65:2406–11.PubMedCrossRef
Metadaten
Titel
Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma
verfasst von
Yisila Mu
Haoshaqiang Zhang
Lixin Che
Kun Li
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0821-3

Weitere Artikel der Ausgabe 2/2014

Medical Oncology 2/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.