Skip to main content
Erschienen in: Clinical and Translational Oncology 11/2014

01.11.2014 | Research Article

TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93

verfasst von: J. Shi, Y. Zhuang, X. K. Liu, Y. X. Zhang, Y. Zhang

Erschienen in: Clinical and Translational Oncology | Ausgabe 11/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

TGF-beta can induce G1 arrest via many mechanisms including up-regulating p21, p27, and Rb. However, as the member of Rb family, whether RBL2 is induced by TGF-beta treatment remains exclusive.

Methods

The expression of RBL2 and miR-93 after TGF-beta treatment was determined by quantitative real-time PCR and western blot. The growth of renal cancer cells was determined by CCK-8 assays and cell cycle was determined by PI staining. The binding of miR-93 on RBL2 3′-UTR was determined by double luciferase system.

Results

In renal cancer cells, TGF-beta treatment induced expression of RBL2 in a time- and concentration-dependent manner, and RBL2 mediated TGF-beta induced growth inhibition and cell cycle arrest in renal cancer cells. Furthermore, we found that miR-93 directly targeted RBL2 by binding to its 3′-UTR in renal cancer cells. Over-expression of miR-93 significantly reduced the expression of RBL2, whereas knock down of miR-93 up-regulated the expression of RBL2. More importantly, TGF-beta treatment inhibited miR-93 expression, which resulted in up-regulation of RBL2 after TGF-beta treatment.

Conclusion

TGF-beta induced RBL2 expression through down-regulating miR-93 in renal cancer cells. The newly identified TGF-beta/miR-93/RBL2 signal pathway reveals a new mechanism of TGF-beta induced growth arrest in renal cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Roberts AB. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 1998;24:111–9.PubMedCrossRef Roberts AB. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 1998;24:111–9.PubMedCrossRef
2.
Zurück zum Zitat Brizzi MF, Dentelli P, Rosso A, Calvi C, Gambino R, Cassader M, et al. RAGE- and TGF-beta receptor-mediated signals converge on STAT5 and p21waf to control cell-cycle progression of mesangial cells: a possible role in the development and progression of diabetic nephropathy. FASEB J. 2004;18:1249–51.PubMed Brizzi MF, Dentelli P, Rosso A, Calvi C, Gambino R, Cassader M, et al. RAGE- and TGF-beta receptor-mediated signals converge on STAT5 and p21waf to control cell-cycle progression of mesangial cells: a possible role in the development and progression of diabetic nephropathy. FASEB J. 2004;18:1249–51.PubMed
3.
Zurück zum Zitat Wolf G, Schroeder R, Zahner G, Stahl RA, Shankland SJ. High glucose-induced hypertrophy of mesangial cells requires p27(Kip1), an inhibitor of cyclin-dependent kinases. Am J Pathol. 2001;158:1091–100.PubMedCrossRefPubMedCentral Wolf G, Schroeder R, Zahner G, Stahl RA, Shankland SJ. High glucose-induced hypertrophy of mesangial cells requires p27(Kip1), an inhibitor of cyclin-dependent kinases. Am J Pathol. 2001;158:1091–100.PubMedCrossRefPubMedCentral
4.
Zurück zum Zitat Galliher AJ, Neil JR, Schiemann WP. Role of transforming growth factor beta in cancer progression. Future Oncol. 2006;2:743–63.PubMedCrossRef Galliher AJ, Neil JR, Schiemann WP. Role of transforming growth factor beta in cancer progression. Future Oncol. 2006;2:743–63.PubMedCrossRef
5.
Zurück zum Zitat Sengupta S, Kundu S, Bhattacharyya A. Attenuation of Smad2 activity shows resistance to TGF-β signalling in mammary adenocarcinoma (MCF-7) cells. Cell Biol Int. 2013;37:449–57.PubMedCrossRef Sengupta S, Kundu S, Bhattacharyya A. Attenuation of Smad2 activity shows resistance to TGF-β signalling in mammary adenocarcinoma (MCF-7) cells. Cell Biol Int. 2013;37:449–57.PubMedCrossRef
7.
Zurück zum Zitat Drabsch Y, ten Dijke P. TGF-β signalling and its role in cancer progression and metastasis. Cancer Metastasis Rev. 2012;31:553–68.PubMedCrossRef Drabsch Y, ten Dijke P. TGF-β signalling and its role in cancer progression and metastasis. Cancer Metastasis Rev. 2012;31:553–68.PubMedCrossRef
8.
Zurück zum Zitat Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271:350–3.PubMedCrossRef Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271:350–3.PubMedCrossRef
9.
Zurück zum Zitat Ramp U, Jaquet K, Reinecke P, Nitsch T, Gabbert HE, Gerharz CD. Acquisition of TGF-beta 1 resistance: an important progression factor in human renal cell carcinoma. Lab Invest. 1997;76:739–49.PubMed Ramp U, Jaquet K, Reinecke P, Nitsch T, Gabbert HE, Gerharz CD. Acquisition of TGF-beta 1 resistance: an important progression factor in human renal cell carcinoma. Lab Invest. 1997;76:739–49.PubMed
10.
Zurück zum Zitat Shang D, Liu Y, Yang P, Chen Y, Tian Y. TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel–Lindau tumor suppressor. Urology. 2012;79:966.e1–7.CrossRef Shang D, Liu Y, Yang P, Chen Y, Tian Y. TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel–Lindau tumor suppressor. Urology. 2012;79:966.e1–7.CrossRef
11.
Zurück zum Zitat Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, et al. Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011;286:8655–65.PubMedCrossRefPubMedCentral Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, et al. Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011;286:8655–65.PubMedCrossRefPubMedCentral
12.
Zurück zum Zitat Ewen ME. p53-dependent repression of cdk4 synthesis in transforming growth factor-beta-induced G1 cell cycle arrest. J Lab Clin Med. 1996;128:355–60.PubMedCrossRef Ewen ME. p53-dependent repression of cdk4 synthesis in transforming growth factor-beta-induced G1 cell cycle arrest. J Lab Clin Med. 1996;128:355–60.PubMedCrossRef
13.
Zurück zum Zitat Choi HH, Jong HS, Hyun Song S, You Kim T, Kyeong Kim N, Bang YJ. p130 mediates TGF-beta-induced cell-cycle arrest in Rb mutant HT-3 cells. Gynecol Oncol. 2002;86:184–9.PubMedCrossRef Choi HH, Jong HS, Hyun Song S, You Kim T, Kyeong Kim N, Bang YJ. p130 mediates TGF-beta-induced cell-cycle arrest in Rb mutant HT-3 cells. Gynecol Oncol. 2002;86:184–9.PubMedCrossRef
14.
Zurück zum Zitat Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376–85.PubMedCrossRef Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376–85.PubMedCrossRef
15.
Zurück zum Zitat Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.PubMedCrossRef Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.PubMedCrossRef
16.
Zurück zum Zitat Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res. 1997;71:165–207.PubMedCrossRef Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res. 1997;71:165–207.PubMedCrossRef
17.
Zurück zum Zitat Lewis BP, Burge CP, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.PubMedCrossRef Lewis BP, Burge CP, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.PubMedCrossRef
18.
Zurück zum Zitat Liang LH, He XH. Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy. Acta Pharmacol Sin. 2011;32:1311–20.PubMedCrossRefPubMedCentral Liang LH, He XH. Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy. Acta Pharmacol Sin. 2011;32:1311–20.PubMedCrossRefPubMedCentral
19.
Zurück zum Zitat Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun. 2011;405:153–6.PubMedCrossRef Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun. 2011;405:153–6.PubMedCrossRef
20.
Zurück zum Zitat Schaefer A, Stephan C, Busch J, Yousef GM, Jung K. Diagnostic, prognostic and therapeutic implications of microRNAs in urologic tumors. Nat Rev Urol. 2010;7:286–97.PubMedCrossRef Schaefer A, Stephan C, Busch J, Yousef GM, Jung K. Diagnostic, prognostic and therapeutic implications of microRNAs in urologic tumors. Nat Rev Urol. 2010;7:286–97.PubMedCrossRef
21.
Zurück zum Zitat Hata A, Davis BN. Control of microRNA biogenesis by TGFbeta signaling pathway—a novel role of Smads in the nucleus. Cytokine Growth Factor Rev. 2009;20:517–21.PubMedCrossRefPubMedCentral Hata A, Davis BN. Control of microRNA biogenesis by TGFbeta signaling pathway—a novel role of Smads in the nucleus. Cytokine Growth Factor Rev. 2009;20:517–21.PubMedCrossRefPubMedCentral
22.
Zurück zum Zitat Petrocca F, Vecchione A, Croce CM. Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191–4.PubMedCrossRef Petrocca F, Vecchione A, Croce CM. Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191–4.PubMedCrossRef
23.
Zurück zum Zitat Huang S, He X, Ding J, Liang L, Zhao Y, Zhang Z, et al. Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 2008;123:972–8.PubMedCrossRef Huang S, He X, Ding J, Liang L, Zhao Y, Zhang Z, et al. Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 2008;123:972–8.PubMedCrossRef
Metadaten
Titel
TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93
verfasst von
J. Shi
Y. Zhuang
X. K. Liu
Y. X. Zhang
Y. Zhang
Publikationsdatum
01.11.2014
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 11/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1185-7

Weitere Artikel der Ausgabe 11/2014

Clinical and Translational Oncology 11/2014 Zur Ausgabe

Update Onkologie

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