Skip to main content
Erschienen in: Tumor Biology 12/2015

01.12.2015 | Research Article

RETRACTED ARTICLE: MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma

verfasst von: Wei Zhang, Kai Liu, Songyang Liu, Bai Ji, Yingchao Wang, Yahui Liu

Erschienen in: Tumor Biology | Ausgabe 12/2015

Einloggen, um Zugang zu erhalten

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs and have critical roles in tumorigenesis and metastasis. A growing body of evidence showed that microRNA-133a (miR-133a) was downregulated and played tumor suppressor roles in gastric, colorectal, bladder, and lung cancer. However, the role and underlying molecular mechanism of miR-133a in hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed the expression of miR-133a in HCC tissues and HCC cell lines. We find that miR-133a was downregulated in HCC tissues and cell lines and that miR-133a expression negatively correlated with tumor differentiation (P < 0.01), TNM stage (P < 0.01), and lymph node metastasis (P < 0.01). Then, functional studies demonstrate that restoration of miR-133a in HepG2 cells significantly suppressed proliferation, colony formation, migration, and invasion, induced cell cycle arrest at G0/G1 stage and cell apoptosis in vitro, and decreased tumor size and weight in a nude mouse HepG2 xenograft model. Using bioinformatics method and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF-1R) as a direct target of miR-133a in HCC cells. Furthermore, overexpression of miR-133a inhibited activation AKT and ERK signal pathway, which contributed to suppression of HCC cell growth. These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of HCC cells by targeting IGF-1R.
Literatur
1.
Zurück zum Zitat Waly Raphael S, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012;2012:421673.PubMedPubMedCentral Waly Raphael S, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012;2012:421673.PubMedPubMedCentral
2.
Zurück zum Zitat Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.CrossRef Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.CrossRef
3.
Zurück zum Zitat Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127:S5–16.CrossRef Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127:S5–16.CrossRef
4.
Zurück zum Zitat Zhou YM, Zhang XF, Yu F, Liu XB, Wu LP, Li B, et al. Efficacy of surgical resection for pulmonary metastases from hepatocellular carcinoma. Med Sci Monit Int Med J Exp Clin Res. 2014;20:1544–9. Zhou YM, Zhang XF, Yu F, Liu XB, Wu LP, Li B, et al. Efficacy of surgical resection for pulmonary metastases from hepatocellular carcinoma. Med Sci Monit Int Med J Exp Clin Res. 2014;20:1544–9.
5.
Zurück zum Zitat Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol WJG. 2014;20:4115–27.CrossRef Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol WJG. 2014;20:4115–27.CrossRef
6.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRef Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRef
7.
Zurück zum Zitat Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.CrossRef Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.CrossRef
8.
Zurück zum Zitat Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14:535–48.CrossRef Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14:535–48.CrossRef
9.
Zurück zum Zitat Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.CrossRef Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.CrossRef
10.
Zurück zum Zitat Zhang X, Han C, He J. Research progress of oncogene and tumor suppressor gene in bladder cancer. Panminerva Med. 2015. Zhang X, Han C, He J. Research progress of oncogene and tumor suppressor gene in bladder cancer. Panminerva Med. 2015.
11.
Zurück zum Zitat Tian T, Wang J, Zhou X. A review: microRNA detection methods. Org Biomol Chem. 2015;13:2226–38.CrossRef Tian T, Wang J, Zhou X. A review: microRNA detection methods. Org Biomol Chem. 2015;13:2226–38.CrossRef
12.
Zurück zum Zitat Saumet A, Mathelier A, Lecellier CH. The potential of microRNAs in personalized medicine against cancers. BioMed Res Int. 2014;2014:642916.CrossRef Saumet A, Mathelier A, Lecellier CH. The potential of microRNAs in personalized medicine against cancers. BioMed Res Int. 2014;2014:642916.CrossRef
13.
Zurück zum Zitat Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev. 2015;81:75–93.CrossRef Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev. 2015;81:75–93.CrossRef
14.
Zurück zum Zitat Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20:460–9.CrossRef Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20:460–9.CrossRef
15.
Zurück zum Zitat Yu H, Lu Y, Li Z, Wang Q. MicroRNA-133: expression, function and therapeutic potential in muscle diseases and cancer. Curr Drug Targets. 2014;15:817–28.CrossRef Yu H, Lu Y, Li Z, Wang Q. MicroRNA-133: expression, function and therapeutic potential in muscle diseases and cancer. Curr Drug Targets. 2014;15:817–28.CrossRef
16.
Zurück zum Zitat Feng Y, Niu LL, Wei W, Zhang WY, Li XY, Cao JH, et al. A feedback circuit between miR-133 and the erk1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation. Cell Death Dis. 2013;4:e934.CrossRef Feng Y, Niu LL, Wei W, Zhang WY, Li XY, Cao JH, et al. A feedback circuit between miR-133 and the erk1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation. Cell Death Dis. 2013;4:e934.CrossRef
17.
Zurück zum Zitat Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, et al. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012;106:405–13.CrossRef Kojima S, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nohata N, et al. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012;106:405–13.CrossRef
18.
Zurück zum Zitat Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, et al. miR-145 and miR-133a function as tumour suppressors and directly regulate fscn1 expression in bladder cancer. Br J Cancer. 2010;102:883–91.CrossRef Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, et al. miR-145 and miR-133a function as tumour suppressors and directly regulate fscn1 expression in bladder cancer. Br J Cancer. 2010;102:883–91.CrossRef
19.
Zurück zum Zitat Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H, et al. Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol. 2011;38:209–17.PubMed Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H, et al. Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol. 2011;38:209–17.PubMed
20.
Zurück zum Zitat Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, et al. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target fscn1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804–14.CrossRef Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, et al. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target fscn1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804–14.CrossRef
21.
Zurück zum Zitat Dong Y, Zhao J, Wu CW, Zhang L, Liu X, Kang W, et al. Tumor suppressor functions of miR-133a in colorectal cancer. Mol Cancer Res MCR. 2013;11:1051–60.CrossRef Dong Y, Zhao J, Wu CW, Zhang L, Liu X, Kang W, et al. Tumor suppressor functions of miR-133a in colorectal cancer. Mol Cancer Res MCR. 2013;11:1051–60.CrossRef
22.
Zurück zum Zitat Ma J, Wang T, Guo R, Yang X, Yin J, Yu J, et al. Involvement of miR-133a and miR-326 in ADM resistance of HepG2 through modulating expression of abcc1. J Drug Target. 2015;25:1–6. Ma J, Wang T, Guo R, Yang X, Yin J, Yu J, et al. Involvement of miR-133a and miR-326 in ADM resistance of HepG2 through modulating expression of abcc1. J Drug Target. 2015;25:1–6.
23.
Zurück zum Zitat Wan TM, Lam CS, Ng L, Chow AK, Wong SK, Li HS, et al. The clinicopathological significance of miR-133a in colorectal cancer. Dis Markers. 2014;2014:919283.CrossRef Wan TM, Lam CS, Ng L, Chow AK, Wong SK, Li HS, et al. The clinicopathological significance of miR-133a in colorectal cancer. Dis Markers. 2014;2014:919283.CrossRef
24.
Zurück zum Zitat Chun YS, Huang M, Rink L, Von Mehren M. Expression levels of insulin-like growth factors and receptors in hepatocellular carcinoma: a retrospective study. World J Surg Oncol. 2014;12:231.CrossRef Chun YS, Huang M, Rink L, Von Mehren M. Expression levels of insulin-like growth factors and receptors in hepatocellular carcinoma: a retrospective study. World J Surg Oncol. 2014;12:231.CrossRef
25.
Zurück zum Zitat Wu J, Zhu AX. Targeting insulin-like growth factor axis in hepatocellular carcinoma. J Hematol Oncol. 2011;4:30.CrossRef Wu J, Zhu AX. Targeting insulin-like growth factor axis in hepatocellular carcinoma. J Hematol Oncol. 2011;4:30.CrossRef
26.
Zurück zum Zitat Osaki LH, Gama P. MAPKs and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 2013;14:10143–61.CrossRef Osaki LH, Gama P. MAPKs and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 2013;14:10143–61.CrossRef
27.
Zurück zum Zitat Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B, Jiang BH. Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 2007;19:1542–53.CrossRef Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B, Jiang BH. Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 2007;19:1542–53.CrossRef
28.
Zurück zum Zitat Oishi N, Yamashita T, Kaneko S. Molecular biology of liver cancer stem cells. Liver Cancer. 2014;3:71–84.CrossRef Oishi N, Yamashita T, Kaneko S. Molecular biology of liver cancer stem cells. Liver Cancer. 2014;3:71–84.CrossRef
29.
Zurück zum Zitat Khare S, Zhang Q, Ibdah JA. Epigenetics of hepatocellular carcinoma: role of microRNA. World J Gastroenterol WJG. 2013;19:5439–45.CrossRef Khare S, Zhang Q, Ibdah JA. Epigenetics of hepatocellular carcinoma: role of microRNA. World J Gastroenterol WJG. 2013;19:5439–45.CrossRef
30.
Zurück zum Zitat Gramantieri L, Fornari F, Callegari E, Sabbioni S, Lanza G, Croce CM, et al. MicroRNA involvement in hepatocellular carcinoma. J Cell Mol Med. 2008;12:2189–204.CrossRef Gramantieri L, Fornari F, Callegari E, Sabbioni S, Lanza G, Croce CM, et al. MicroRNA involvement in hepatocellular carcinoma. J Cell Mol Med. 2008;12:2189–204.CrossRef
31.
Zurück zum Zitat Negrini M, Gramantieri L, Sabbioni S, Croce CM. MicroRNA involvement in hepatocellular carcinoma. Anti Cancer Agents Med Chem. 2011;11:500–21.CrossRef Negrini M, Gramantieri L, Sabbioni S, Croce CM. MicroRNA involvement in hepatocellular carcinoma. Anti Cancer Agents Med Chem. 2011;11:500–21.CrossRef
32.
Zurück zum Zitat Qiu T, Zhou X, Wang J, Du Y, Xu J, Huang Z, et al. miR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer. FEBS Lett. 2014;588:1168–77.CrossRef Qiu T, Zhou X, Wang J, Du Y, Xu J, Huang Z, et al. miR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer. FEBS Lett. 2014;588:1168–77.CrossRef
33.
Zurück zum Zitat Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, et al. Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of coronin1c. J Hum Genet. 2015;60:53–61.CrossRef Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, et al. Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of coronin1c. J Hum Genet. 2015;60:53–61.CrossRef
34.
Zurück zum Zitat Ji F, Zhang H, Wang Y, Li M, Xu W, Kang Y, et al. MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xl and Mcl-1. Bone. 2013;56:220–6.CrossRef Ji F, Zhang H, Wang Y, Li M, Xu W, Kang Y, et al. MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xl and Mcl-1. Bone. 2013;56:220–6.CrossRef
35.
Zurück zum Zitat King H, Aleksic T, Haluska P, Macaulay VM. Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 2014;40:1096–105.CrossRef King H, Aleksic T, Haluska P, Macaulay VM. Can we unlock the potential of IGF-1R inhibition in cancer therapy? Cancer Treat Rev. 2014;40:1096–105.CrossRef
36.
Zurück zum Zitat Scharf JG, Braulke T. The role of the igf axis in hepatocarcinogenesis. Horm Metab Res Horm Stoffwechselforschung Horm Metab. 2003;35:685–93.CrossRef Scharf JG, Braulke T. The role of the igf axis in hepatocarcinogenesis. Horm Metab Res Horm Stoffwechselforschung Horm Metab. 2003;35:685–93.CrossRef
37.
Zurück zum Zitat Singh P, Alex JM, Bast F. Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: novel treatment strategies for cancer. Med Oncol. 2014;31:805.CrossRef Singh P, Alex JM, Bast F. Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: novel treatment strategies for cancer. Med Oncol. 2014;31:805.CrossRef
38.
Zurück zum Zitat Wang LK, Hsiao TH, Hong TM, Chen HY, Kao SH, Wang WL, et al. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. PLoS One. 2014;9:e96765.CrossRef Wang LK, Hsiao TH, Hong TM, Chen HY, Kao SH, Wang WL, et al. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. PLoS One. 2014;9:e96765.CrossRef
39.
Zurück zum Zitat Gong Y, Ren J, Liu K, Tang LM. Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R. World J Gastroenterol WJG. 2015;21:2949–58.CrossRef Gong Y, Ren J, Liu K, Tang LM. Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R. World J Gastroenterol WJG. 2015;21:2949–58.CrossRef
40.
Zurück zum Zitat Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y, et al. MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:11269–75.CrossRef Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y, et al. MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:11269–75.CrossRef
Metadaten
Titel
RETRACTED ARTICLE: MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma
verfasst von
Wei Zhang
Kai Liu
Songyang Liu
Bai Ji
Yingchao Wang
Yahui Liu
Publikationsdatum
01.12.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3749-8

Weitere Artikel der Ausgabe 12/2015

Tumor Biology 12/2015 Zur Ausgabe

Update Onkologie

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