Skip to main content
Erschienen in: Tumor Biology 2/2014

01.02.2014 | Research Article

MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61

verfasst von: Jianhua Huang, Kanda Gao, Jian Lin, Qiugen Wang

Erschienen in: Tumor Biology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Increasing evidence indicates that microRNAs (miRNAs) participate in almost every step of cellular processes and are often aberrantly expressed in human cancer. Therefore, the discovery of miRNAs may provide a new and powerful tool for understanding the mechanism and treatment of carcinogenesis. The aim of this study was to investigate the functional significance of miR-100 and to identify its possible target genes in osteosarcoma (OS) cells. Here, we found that expression level of miR-100 was significantly decreased in osteosarcoma tissues in comparison with the adjacent normal tissues. The enforced expression of miR-100 was able to inhibit cell proliferation in Saos-2 and MG63 cells, while its antisense oligonucleotides (antisense miR-100) promoted cell proliferation. Moreover, our results further revealed that expression of Cyr61, an extracellular matrix-associated growth factor, was negatively regulated by miR-100. Therefore, we consider that miR-100 acts as a tumor suppressor for osteosarcoma. It may provide novel diagnostic and therapeutic options for human osteosarcoma in the future.
Literatur
1.
Zurück zum Zitat Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.PubMedCrossRef Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.PubMedCrossRef
2.
Zurück zum Zitat Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14(8):475–88.PubMedCrossRef Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14(8):475–88.PubMedCrossRef
3.
Zurück zum Zitat van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56.PubMedCrossRef van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56.PubMedCrossRef
4.
Zurück zum Zitat Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11(12):849–64.PubMedCrossRef Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11(12):849–64.PubMedCrossRef
5.
Zurück zum Zitat Liang W, Gao B, Fu P, Xu S, Qian Y, Fu Q. The miRNAs in the pathogenesis 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 pathogenesis of osteosarcoma. Front Biosci. 2013;18:788–94.CrossRef
6.
Zurück zum Zitat Cai CK, Zhao GY, Tian LY, Liu L, Yan K, Ma YL, et al. miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep. 2012;28(5):1764–70.PubMed Cai CK, Zhao GY, Tian LY, Liu L, Yan K, Ma YL, et al. miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep. 2012;28(5):1764–70.PubMed
7.
Zurück zum Zitat Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res. 2012;72(4):908–16.PubMedCentralPubMedCrossRef Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res. 2012;72(4):908–16.PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat 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.PubMed 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.PubMed
9.
Zurück zum Zitat Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46.PubMedCrossRef Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46.PubMedCrossRef
10.
Zurück zum Zitat Liu J, Lu KH, Liu ZL, Sun M, De W, Wang ZX. MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1. BMC Cancer. 2012;12:519.PubMedCentralPubMedCrossRef Liu J, Lu KH, Liu ZL, Sun M, De W, Wang ZX. MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1. BMC Cancer. 2012;12:519.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Chen P, Zhao X, Ma L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013. doi:10.1007/s11010-013-1753-0. Chen P, Zhao X, Ma L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013. doi:10.​1007/​s11010-013-1753-0.
12.
Zurück zum Zitat Petrelli A, Perra A, Schernhuber K, Cargnelutti M, Salvi A, Migliore C, et al. Sequential analysis of multistage hepatocarcinogenesis reveals that miR-100 and PLK1 dysregulation is an early event maintained along tumor progression. Oncogene. 2012;31(42):4517–26.PubMedCrossRef Petrelli A, Perra A, Schernhuber K, Cargnelutti M, Salvi A, Migliore C, et al. Sequential analysis of multistage hepatocarcinogenesis reveals that miR-100 and PLK1 dysregulation is an early event maintained along tumor progression. Oncogene. 2012;31(42):4517–26.PubMedCrossRef
13.
Zurück zum Zitat Gebeshuber CA, Martinez J. miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling. Oncogene. 2013;32(27):3306–10.PubMedCrossRef Gebeshuber CA, Martinez J. miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling. Oncogene. 2013;32(27):3306–10.PubMedCrossRef
14.
Zurück zum Zitat Bai J, Guo A, Hong Z, Kuai W. Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia. Onco Targets Ther. 2012;5:213–9.PubMedCentralPubMed Bai J, Guo A, Hong Z, Kuai W. Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia. Onco Targets Ther. 2012;5:213–9.PubMedCentralPubMed
15.
Zurück zum Zitat Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92.PubMedCentralPubMedCrossRef Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92.PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Lee KB, Byun HJ, Park SH, Park CY, Lee SH, Rho SB. CYR61 controls p53 and NF-κB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. Cancer Lett. 2012;315(1):86–95.PubMedCrossRef Lee KB, Byun HJ, Park SH, Park CY, Lee SH, Rho SB. CYR61 controls p53 and NF-κB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. Cancer Lett. 2012;315(1):86–95.PubMedCrossRef
18.
Zurück zum Zitat Goodwin CR, Lal B, Zhou X, Ho S, Xia S, Taeger A, et al. Cyr61 mediates hepatocyte growth factor-dependent tumor cell growth, migration, and Akt activation. Cancer Res. 2010;70(7):2932–41.PubMedCentralPubMedCrossRef Goodwin CR, Lal B, Zhou X, Ho S, Xia S, Taeger A, et al. Cyr61 mediates hepatocyte growth factor-dependent tumor cell growth, migration, and Akt activation. Cancer Res. 2010;70(7):2932–41.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Lin J, Huo R, Wang L, Zhou Z, Sun Y, Shen B, et al. A novel anti-Cyr61 antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol Immunother. 2012;61(5):677–87.PubMedCrossRef Lin J, Huo R, Wang L, Zhou Z, Sun Y, Shen B, et al. A novel anti-Cyr61 antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol Immunother. 2012;61(5):677–87.PubMedCrossRef
20.
Zurück zum Zitat Tsai MS, Bogart DF, Li P, Mehmi I, Lupu R. Expression and regulation of Cyr61 in human breast cancer cell lines. Oncogene. 2002;21(6):964–73.PubMedCrossRef Tsai MS, Bogart DF, Li P, Mehmi I, Lupu R. Expression and regulation of Cyr61 in human breast cancer cell lines. Oncogene. 2002;21(6):964–73.PubMedCrossRef
22.
Zurück zum Zitat Haque I, Mehta S, Majumder M, Dhar K, De A, McGregor D, et al. Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis. Mol Cancer. 2011;10:8.PubMedCentralPubMedCrossRef Haque I, Mehta S, Majumder M, Dhar K, De A, McGregor D, et al. Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis. Mol Cancer. 2011;10:8.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Xie JJ, Xu LY, Xie YM, Du ZP, Feng CH, Dong H, et al. Involvement of Cyr61 in the growth, invasiveness and adhesion of esophageal squamous cell carcinoma cells. Int J Mol Med. 2011;27(3):429–34.PubMed Xie JJ, Xu LY, Xie YM, Du ZP, Feng CH, Dong H, et al. Involvement of Cyr61 in the growth, invasiveness and adhesion of esophageal squamous cell carcinoma cells. Int J Mol Med. 2011;27(3):429–34.PubMed
24.
Zurück zum Zitat Sabile AA, Arlt MJ, Muff R, Bode B, Langsam B, Bertz J, et al. Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice. J Bone Miner Res. 2012;27(1):58–67.PubMedCrossRef Sabile AA, Arlt MJ, Muff R, Bode B, Langsam B, Bertz J, et al. Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice. J Bone Miner Res. 2012;27(1):58–67.PubMedCrossRef
25.
Zurück zum Zitat Fromigue O, Hamidouche Z, Vaudin P, Lecanda F, Patino A, Barbry P, et al. CYR61 downregulation reduces osteosarcoma cell invasion, migration, and metastasis. J Bone Miner Res. 2011;26(7):1533–42.PubMedCrossRef Fromigue O, Hamidouche Z, Vaudin P, Lecanda F, Patino A, Barbry P, et al. CYR61 downregulation reduces osteosarcoma cell invasion, migration, and metastasis. J Bone Miner Res. 2011;26(7):1533–42.PubMedCrossRef
Metadaten
Titel
MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61
verfasst von
Jianhua Huang
Kanda Gao
Jian Lin
Qiugen Wang
Publikationsdatum
01.02.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1146-8

Weitere Artikel der Ausgabe 2/2014

Tumor Biology 2/2014 Zur Ausgabe

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Onkologie

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