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Published in: Pathology & Oncology Research 2/2019

Open Access 01-04-2019 | Original Article

Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and their Clinical Implications

Authors: Lei Wang, Ailixiati Aireti, Aizezi Aihaiti, Kun Li

Published in: Pathology & Oncology Research | Issue 2/2019

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Abstract

Previous study revealed that microRNA (miR)-150 might function as a tumor suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in 20 osteosarcoma and matched adjacent noncancerous tissues were respectively detected by quantitative real-time PCR and western blot analyses. Then, subcellular localization and expression pattern of IGF2BP1 protein in 100 osteosarcoma tissues were examined by immunohistochemistry. Associations of miR-150/IGF2BP1 expression with various clinicopathological features and patients’ prognosis were also statistically evaluated. As a result, miR-150 expression was significantly decreased, while IGF2BP1 mRNA and protein expression were dramatically increased in osteosarcoma tissues compared to matched adjacent noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all significantly associated with high tumor grade, presence of metastasis and recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover, miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as independent prognostic factors for overall and disease-free survivals of osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR-150 and its downstream target IGF2BP1 may be a crucial axis for the development, progression and patients’ prognosis of ostesarcoma. The newly identified miR-150/IGF2BP1 axis might be a novel potential therapeutic target for osteosarcoma treatment.
Literature
1.
go back to reference Fagioli F, Biasin E, Mereuta OM, Muraro M, Luksch R, Ferrari S, Aglietta M, Madon E (2008) Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant 41(Suppl 2):S131–S134CrossRefPubMed Fagioli F, Biasin E, Mereuta OM, Muraro M, Luksch R, Ferrari S, Aglietta M, Madon E (2008) Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant 41(Suppl 2):S131–S134CrossRefPubMed
2.
go back to reference Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K (1996) Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol 14:848–858CrossRefPubMed Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K (1996) Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol 14:848–858CrossRefPubMed
5.
go back to reference Piletič K, Kunej T (2016) MicroRNA epigenetic signatures in human disease. Arch Toxicol 90:2405–2419CrossRefPubMed Piletič K, Kunej T (2016) MicroRNA epigenetic signatures in human disease. Arch Toxicol 90:2405–2419CrossRefPubMed
6.
go back to reference Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222CrossRefPubMed Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222CrossRefPubMed
7.
8.
go back to reference Makarova JA, Shkurnikov MU, Wicklein D, Lange T, Samatov TR, Turchinovich AA, Tonevitsky AG (2016) Intracellular and extracellular microRNA: an update on localization and biological role. Prog Histochem Cytochem 51:33–49CrossRefPubMed Makarova JA, Shkurnikov MU, Wicklein D, Lange T, Samatov TR, Turchinovich AA, Tonevitsky AG (2016) Intracellular and extracellular microRNA: an update on localization and biological role. Prog Histochem Cytochem 51:33–49CrossRefPubMed
9.
go back to reference Ram Kumar RM, Boro A, Fuchs B (2016) Involvement and clinical aspects of MicroRNA in osteosarcoma. Int J Mol Sci 17:E877CrossRefPubMed Ram Kumar RM, Boro A, Fuchs B (2016) Involvement and clinical aspects of MicroRNA in osteosarcoma. Int J Mol Sci 17:E877CrossRefPubMed
11.
go back to reference Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J (2010) The role of microRNAs in normal and malignant hematopoiesis. Eur J Haematol 84:1–16CrossRefPubMed Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J (2010) The role of microRNAs in normal and malignant hematopoiesis. Eur J Haematol 84:1–16CrossRefPubMed
13.
go back to reference Li X, Chen L, Wang W, Meng FB, Zhao RT, Chen Y (2015) MicroRNA-150 inhibits cell invasion and migration and is downregulated in human osteosarcoma. Cytogenet Genome Res 146:124–135CrossRefPubMed Li X, Chen L, Wang W, Meng FB, Zhao RT, Chen Y (2015) MicroRNA-150 inhibits cell invasion and migration and is downregulated in human osteosarcoma. Cytogenet Genome Res 146:124–135CrossRefPubMed
14.
go back to reference Zhan C, Li C, Zhang H, Tang H, Ji F, Qiao SC, Xu WD, Wang ZW (2016) MicroRNA-150 upregulation reduces osteosarcoma cell invasion and metastasis by downregulating Ezrin. Oncol Lett 12:3457–3462CrossRefPubMedPubMedCentral Zhan C, Li C, Zhang H, Tang H, Ji F, Qiao SC, Xu WD, Wang ZW (2016) MicroRNA-150 upregulation reduces osteosarcoma cell invasion and metastasis by downregulating Ezrin. Oncol Lett 12:3457–3462CrossRefPubMedPubMedCentral
15.
go back to reference Wang L, Wang W, Li J, Chen S, Zhan R (2016) MicroRNA-150 inhibits osteosarcoma cell proliferation by targeting RUNX2 gene. Zhong Nan Da Xue Xue Bao Yi Xue Ban 41:1285–1290PubMed Wang L, Wang W, Li J, Chen S, Zhan R (2016) MicroRNA-150 inhibits osteosarcoma cell proliferation by targeting RUNX2 gene. Zhong Nan Da Xue Xue Bao Yi Xue Ban 41:1285–1290PubMed
16.
go back to reference Qu Y, Pan S, Kang M, Dong R, Zhao J (2016) MicroRNA-150 functions as a tumor suppressor in osteosarcoma by targeting IGF2BP1. Tumour Biol 37:5275–5284CrossRefPubMed Qu Y, Pan S, Kang M, Dong R, Zhao J (2016) MicroRNA-150 functions as a tumor suppressor in osteosarcoma by targeting IGF2BP1. Tumour Biol 37:5275–5284CrossRefPubMed
18.
go back to reference Zhao J, Xu H, He M, Wu Y (2014) Glucocorticoid receptor DNA binding factor 1 expression and osteosarcoma prognosis. Tumour Biol 35:12449–12458CrossRefPubMed Zhao J, Xu H, He M, Wu Y (2014) Glucocorticoid receptor DNA binding factor 1 expression and osteosarcoma prognosis. Tumour Biol 35:12449–12458CrossRefPubMed
19.
go back to reference Liao Y, Feng Y, Shen J, Gao Y, Cote G, Choy E, Harmon D, Mankin H, Hornicek F, Duan Z (2016) Clinical and biological significance of PIM1 kinase in osteosarcoma. J Orthop Res 34:1185–1194CrossRefPubMed Liao Y, Feng Y, Shen J, Gao Y, Cote G, Choy E, Harmon D, Mankin H, Hornicek F, Duan Z (2016) Clinical and biological significance of PIM1 kinase in osteosarcoma. J Orthop Res 34:1185–1194CrossRefPubMed
20.
go back to reference Abd El-Rehim DM, Osman NA (2015) Expression of a disintegrin and metalloprotease 8 and endostatin in human osteosarcoma: implication in tumor progression and prognosis. J Egypt Natl Canc Inst 27:1–9CrossRefPubMed Abd El-Rehim DM, Osman NA (2015) Expression of a disintegrin and metalloprotease 8 and endostatin in human osteosarcoma: implication in tumor progression and prognosis. J Egypt Natl Canc Inst 27:1–9CrossRefPubMed
21.
go back to reference Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, Kume M, Kameoka Y, Takahashi N, Nakagawa T, Shimizu N, Sawada K (2011) The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia 25:1324–1334CrossRefPubMed Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, Kume M, Kameoka Y, Takahashi N, Nakagawa T, Shimizu N, Sawada K (2011) The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia 25:1324–1334CrossRefPubMed
22.
go back to reference Sakr M, Takino T, Sabit H, Nakada M, Li Z, Sato H (2016) miR-150-5p and miR-133a suppress glioma cell proliferation and migration through targeting membrane-type-1 matrix metalloproteinase. Gene 587:155–162CrossRefPubMed Sakr M, Takino T, Sabit H, Nakada M, Li Z, Sato H (2016) miR-150-5p and miR-133a suppress glioma cell proliferation and migration through targeting membrane-type-1 matrix metalloproteinase. Gene 587:155–162CrossRefPubMed
23.
go back to reference Wang X, Ren Y, Wang Z, Xiong X, Han S, Pan W, Chen H, Zhou L, Zhou C, Yuan Q, Yang M (2015) Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells. FEBS Lett 589(24 Pt B):3989–3997CrossRefPubMed Wang X, Ren Y, Wang Z, Xiong X, Han S, Pan W, Chen H, Zhou L, Zhou C, Yuan Q, Yang M (2015) Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells. FEBS Lett 589(24 Pt B):3989–3997CrossRefPubMed
24.
go back to reference Huang S, Chen Y, Wu W, Ouyang N, Chen J, Li H, Liu X, Su F, Lin L, Yao Y (2013) miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 8:e80707CrossRefPubMedPubMedCentral Huang S, Chen Y, Wu W, Ouyang N, Chen J, Li H, Liu X, Su F, Lin L, Yao Y (2013) miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 8:e80707CrossRefPubMedPubMedCentral
25.
go back to reference Li H, Ouyang R, Wang Z, Zhou W, Chen H, Jiang Y, Zhang Y, Li H, Liao M, Wang W, Ye M, Ding Z, Feng X, Liu J, Zhang B (2016) MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4. Sci Rep 6:39001CrossRefPubMedPubMedCentral Li H, Ouyang R, Wang Z, Zhou W, Chen H, Jiang Y, Zhang Y, Li H, Liao M, Wang W, Ye M, Ding Z, Feng X, Liu J, Zhang B (2016) MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4. Sci Rep 6:39001CrossRefPubMedPubMedCentral
26.
go back to reference Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, Ren G, Su T, Pan Y, Feng B, Xue Z, Wang X, Fan D (2010) MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun 392:340–345CrossRefPubMed Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, Ren G, Su T, Pan Y, Feng B, Xue Z, Wang X, Fan D (2010) MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun 392:340–345CrossRefPubMed
27.
go back to reference Wang S, Yin J, Li T, Yuan L, Wang D, He J, Du X, Lu J (2015) Upregulated circulating miR-150 is associated with the risk of intrahepatic cholangiocarcinoma. Oncol Rep 33:819–825CrossRefPubMed Wang S, Yin J, Li T, Yuan L, Wang D, He J, Du X, Lu J (2015) Upregulated circulating miR-150 is associated with the risk of intrahepatic cholangiocarcinoma. Oncol Rep 33:819–825CrossRefPubMed
28.
go back to reference Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Zhan Q, Deng X, Chen H, Shen B, Peng C, Li H, Zhu Z (2014) miR-150-5p inhibits hepatoma cell migration and invasion by targeting MMP14. PLoS One 9:e115577CrossRefPubMedPubMedCentral Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Zhan Q, Deng X, Chen H, Shen B, Peng C, Li H, Zhu Z (2014) miR-150-5p inhibits hepatoma cell migration and invasion by targeting MMP14. PLoS One 9:e115577CrossRefPubMedPubMedCentral
29.
go back to reference Yang K, He M, Cai Z, Ni C, Deng J, Ta N, Xu J, Zheng J (2015) A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4. Pancreas 44:370–379CrossRefPubMed Yang K, He M, Cai Z, Ni C, Deng J, Ta N, Xu J, Zheng J (2015) A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4. Pancreas 44:370–379CrossRefPubMed
30.
go back to reference Aherne ST, Madden SF, Hughes DJ, Pardini B, Naccarati A, Levy M, Vodicka P, Neary P, Dowling P, Clynes M (2015) Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression. BMC Cancer 15:329CrossRefPubMedPubMedCentral Aherne ST, Madden SF, Hughes DJ, Pardini B, Naccarati A, Levy M, Vodicka P, Neary P, Dowling P, Clynes M (2015) Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression. BMC Cancer 15:329CrossRefPubMedPubMedCentral
31.
32.
go back to reference Wuerkenbieke D, Wang J, Li Y, Ma C (2015) miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation. Arch Gynecol Obstet 292:1109–1116CrossRefPubMed Wuerkenbieke D, Wang J, Li Y, Ma C (2015) miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation. Arch Gynecol Obstet 292:1109–1116CrossRefPubMed
33.
go back to reference Liu DZ, Zhang HY, Long XL, Zou SL, Zhang XY, Han GY, Cui ZG (2015) MIR-150 promotes prostate cancer stem cell development via suppressing p27Kip1. Eur Rev Med Pharmacol Sci 19:4344–4352PubMed Liu DZ, Zhang HY, Long XL, Zou SL, Zhang XY, Han GY, Cui ZG (2015) MIR-150 promotes prostate cancer stem cell development via suppressing p27Kip1. Eur Rev Med Pharmacol Sci 19:4344–4352PubMed
34.
go back to reference Yisraeli JK (2005) VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins. Biol Cell 97:87–96CrossRefPubMed Yisraeli JK (2005) VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins. Biol Cell 97:87–96CrossRefPubMed
35.
go back to reference Yaniv K, Yisraeli JK (2002) The involvement of a conserved family of RNA binding proteins in embryonic development and carcinogenesis. Gene 287:49–54CrossRefPubMed Yaniv K, Yisraeli JK (2002) The involvement of a conserved family of RNA binding proteins in embryonic development and carcinogenesis. Gene 287:49–54CrossRefPubMed
36.
go back to reference Gutschner T, Hämmerle M, Pazaitis N, Bley N, Fiskin E, Uckelmann H, Heim A, Groβ M, Hofmann N, Geffers R, Skawran B, Longerich T, Breuhahn K, Schirmacher P, Mühleck B, Hüttelmaier S, Diederichs S (2014) Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma. Hepatology 59:1900–1911CrossRefPubMed Gutschner T, Hämmerle M, Pazaitis N, Bley N, Fiskin E, Uckelmann H, Heim A, Groβ M, Hofmann N, Geffers R, Skawran B, Longerich T, Breuhahn K, Schirmacher P, Mühleck B, Hüttelmaier S, Diederichs S (2014) Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma. Hepatology 59:1900–1911CrossRefPubMed
37.
go back to reference Su Y, Xiong J, Hu J, Wei X, Zhang X, Rao L (2016) MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget 7:68397–68411PubMedPubMedCentral Su Y, Xiong J, Hu J, Wei X, Zhang X, Rao L (2016) MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget 7:68397–68411PubMedPubMedCentral
Metadata
Title
Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and their Clinical Implications
Authors
Lei Wang
Ailixiati Aireti
Aizezi Aihaiti
Kun Li
Publication date
01-04-2019
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-018-0454-0

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