Skip to main content
Erschienen in: Tumor Biology 8/2016

28.01.2016 | Original Article

RETRACTED ARTICLE: miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3

verfasst von: Bo Li, Zhongshi Xie, Bai Li

Erschienen in: Tumor Biology | Ausgabe 8/2016

Einloggen, um Zugang zu erhalten

Abstract

Accumulating evidence showed that microRNA-152 (miR-152) was frequently downregulated, and functioned as tumor suppressor in many cancers, but little is known about its biological role and intrinsic regulatory mechanisms in colorectal cancer (CRC). Here, we explored the potential role of miR-152 in CRC and the possible molecular mechanisms. Our results proved that miR-152 expression was downregulated in CRC cell lines and tissue samples, and its expression was inversely correlated with advanced tumor-node-metastasis (TNM) stage (P < 0.01) and lymph node metastasis (P < 0.01). Function assays demonstrated that restoring the expression of miR-152 in CRC cells dramatically reduced the cell proliferation and cell migration and invasion and promoted apoptosis and caspase-3 activity in vitro, as well as suppressed tumor growth in vivo. Mechanistic investigations defined phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) as a direct and functional downstream target of miR-152. In addition, we also found that PIK3R3 expression was upregulated and was inversely correlated with miR-152 expression in clinical CRC tissues. Downregulation of PIK3R3 mimicked the tumor-suppressive effects of miR-152 overexpression in CRC cells. Taken together, these results elucidated the function of miR-152 in CRC progression and suggested that miR-152 might function as tumor suppressor in CRC by targeting PIK3R3.
Literatur
1.
2.
Zurück zum Zitat Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191–7.CrossRefPubMedPubMedCentral Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191–7.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83–92.PubMedPubMedCentral Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83–92.PubMedPubMedCentral
5.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMed
7.
Zurück zum Zitat Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.CrossRefPubMed Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.CrossRefPubMed
8.
Zurück zum Zitat Amirkhah R, Schmitz U, Linnebacher M, Wolkenhauer O, Farazmand A. MicroRNA-mRNA interactions in colorectal cancer and their role in tumor progression. Genes Chromosomes Cancer. 2015;54:129–41.CrossRefPubMed Amirkhah R, Schmitz U, Linnebacher M, Wolkenhauer O, Farazmand A. MicroRNA-mRNA interactions in colorectal cancer and their role in tumor progression. Genes Chromosomes Cancer. 2015;54:129–41.CrossRefPubMed
9.
Zurück zum Zitat Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol. 2012;59:467–74.CrossRefPubMed Tokarz P, Blasiak J. The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol. 2012;59:467–74.CrossRefPubMed
10.
Zurück zum Zitat Wu Y, Huang A, Li T, Su X, Ding H, Li H, et al. Mir-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting adam17. FEBS Lett. 2014;588:2063–9.CrossRefPubMed Wu Y, Huang A, Li T, Su X, Ding H, Li H, et al. Mir-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting adam17. FEBS Lett. 2014;588:2063–9.CrossRefPubMed
11.
Zurück zum Zitat Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, et al. Altered expression of mir-148a and mir-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 2010;14:1170–9.CrossRefPubMed Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, et al. Altered expression of mir-148a and mir-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 2010;14:1170–9.CrossRefPubMed
12.
Zurück zum Zitat Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y, et al. Altered expression of mir-152 and mir-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 2012;27:447–54.PubMed Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y, et al. Altered expression of mir-152 and mir-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 2012;27:447–54.PubMed
13.
Zurück zum Zitat Tang XL, Lin L, Song LN, Tang XH. Hypoxia-inducible mir-152 suppresses the expression of wnt1 and erbb3, and inhibits the proliferation of cervical cancer cells. Exp Biol Med. 2015. Tang XL, Lin L, Song LN, Tang XH. Hypoxia-inducible mir-152 suppresses the expression of wnt1 and erbb3, and inhibits the proliferation of cervical cancer cells. Exp Biol Med. 2015.
14.
Zurück zum Zitat Huang H, Hu M, Li P, Lu C, Li M. Mir-152 inhibits cell proliferation and colony formation of cd133(+) liver cancer stem cells by targeting kit. Tumour Biol. 2015;36:921–8.CrossRefPubMed Huang H, Hu M, Li P, Lu C, Li M. Mir-152 inhibits cell proliferation and colony formation of cd133(+) liver cancer stem cells by targeting kit. Tumour Biol. 2015;36:921–8.CrossRefPubMed
15.
16.
Zurück zum Zitat Zhai R, Kan X, Wang B, Du H, Long Y, Wu H, et al. Mir-152 suppresses gastric cancer cell proliferation and motility by targeting cd151. Tumour Biol. 2014;35:11367–73.CrossRefPubMed Zhai R, Kan X, Wang B, Du H, Long Y, Wu H, et al. Mir-152 suppresses gastric cancer cell proliferation and motility by targeting cd151. Tumour Biol. 2014;35:11367–73.CrossRefPubMed
17.
Zurück zum Zitat Liu K, Li X, Cao Y, Ge Y, Wang J, Shi B. Mir-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting pik3r3. Int J Oncol. 2015;47:1585–93.CrossRefPubMed Liu K, Li X, Cao Y, Ge Y, Wang J, Shi B. Mir-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting pik3r3. Int J Oncol. 2015;47:1585–93.CrossRefPubMed
18.
Zurück zum Zitat Wu L, Shi B, Huang K, Fan G. Microrna-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting irs1. Oncol Rep. 2015;34:2797–805.CrossRefPubMed Wu L, Shi B, Huang K, Fan G. Microrna-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting irs1. Oncol Rep. 2015;34:2797–805.CrossRefPubMed
19.
Zurück zum Zitat Sheng L, He P, Yang X, Zhou M, Feng Q. Mir-612 negatively regulates colorectal cancer growth and metastasis by targeting akt2. Cell Death Dis. 2015;6:e1808.CrossRefPubMedPubMedCentral Sheng L, He P, Yang X, Zhou M, Feng Q. Mir-612 negatively regulates colorectal cancer growth and metastasis by targeting akt2. Cell Death Dis. 2015;6:e1808.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, et al. Microrna-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer. Oncogene. 2013;32:1910–20.CrossRefPubMed Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, et al. Microrna-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer. Oncogene. 2013;32:1910–20.CrossRefPubMed
21.
Zurück zum Zitat Wang H, Cao F, Li X, Miao H, E J, Xing J, Fu CG. Mir-320b suppresses cell proliferation by targeting c-myc in human colorectal cancer cells. BMC Cancer. 2015;15:748. Wang H, Cao F, Li X, Miao H, E J, Xing J, Fu CG. Mir-320b suppresses cell proliferation by targeting c-myc in human colorectal cancer cells. BMC Cancer. 2015;15:748.
22.
Zurück zum Zitat Chen Z, Liu S, Tian L, Wu M, Ai F, Tang W, et al. Mir-124 and mir-506 inhibit colorectal cancer progression by targeting dnmt3b and dnmt1. Oncotarget. 2015;6:38139–50.CrossRefPubMedPubMedCentral Chen Z, Liu S, Tian L, Wu M, Ai F, Tang W, et al. Mir-124 and mir-506 inhibit colorectal cancer progression by targeting dnmt3b and dnmt1. Oncotarget. 2015;6:38139–50.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Liu DZ, Ander BP, Tian Y, Stamova B, Jickling GC, Davis RR, et al. Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells. Gene. 2012;495:120–7.CrossRefPubMed Liu DZ, Ander BP, Tian Y, Stamova B, Jickling GC, Davis RR, et al. Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells. Gene. 2012;495:120–7.CrossRefPubMed
24.
Zurück zum Zitat Xia X, Cheng A, Akinmade D, Hamburger AW. The n-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest. Mol Cell Biol. 2003;23:1717–25.CrossRefPubMedPubMedCentral Xia X, Cheng A, Akinmade D, Hamburger AW. The n-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest. Mol Cell Biol. 2003;23:1717–25.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Klahan S, Wu MS, Hsi E, Huang CC, Hou MF, Chang WC. Computational analysis of mRNA expression profiles identifies the itg family and pik3r3 as crucial genes for regulating triple negative breast cancer cell migration. BioMed Res Int. 2014;2014:536591.CrossRefPubMedPubMedCentral Klahan S, Wu MS, Hsi E, Huang CC, Hou MF, Chang WC. Computational analysis of mRNA expression profiles identifies the itg family and pik3r3 as crucial genes for regulating triple negative breast cancer cell migration. BioMed Res Int. 2014;2014:536591.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Soroceanu L, Kharbanda S, Chen R, Soriano RH, Aldape K, Misra A, et al. Identification of igf2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc Natl Acad Sci U S A. 2007;104:3466–71.CrossRefPubMedPubMedCentral Soroceanu L, Kharbanda S, Chen R, Soriano RH, Aldape K, Misra A, et al. Identification of igf2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc Natl Acad Sci U S A. 2007;104:3466–71.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Zhang L, Huang J, Yang N, Greshock J, Liang S, Hasegawa K, et al. Integrative genomic analysis of phosphatidylinositol 3′-kinase family identifies pik3r3 as a potential therapeutic target in epithelial ovarian cancer. Clin Cancer Res. 2007;13:5314–21.CrossRefPubMed Zhang L, Huang J, Yang N, Greshock J, Liang S, Hasegawa K, et al. Integrative genomic analysis of phosphatidylinositol 3′-kinase family identifies pik3r3 as a potential therapeutic target in epithelial ovarian cancer. Clin Cancer Res. 2007;13:5314–21.CrossRefPubMed
28.
Zurück zum Zitat Xu L, Wen Z, Zhou Y, Liu Z, Li Q, Fei G, et al. Microrna-7-regulated tlr9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/akt pathway. Mol Biol Cell. 2013;24:42–55.CrossRefPubMedPubMedCentral Xu L, Wen Z, Zhou Y, Liu Z, Li Q, Fei G, et al. Microrna-7-regulated tlr9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/akt pathway. Mol Biol Cell. 2013;24:42–55.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Wang G, Yang X, Li C, Cao X, Luo X, Hu J. Pik3r3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer. Mol Cancer Ther. 2014;13:1837–47.CrossRefPubMed Wang G, Yang X, Li C, Cao X, Luo X, Hu J. Pik3r3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer. Mol Cancer Ther. 2014;13:1837–47.CrossRefPubMed
Metadaten
Titel
RETRACTED ARTICLE: miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3
verfasst von
Bo Li
Zhongshi Xie
Bai Li
Publikationsdatum
28.01.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 8/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4888-2

Weitere Artikel der Ausgabe 8/2016

Tumor Biology 8/2016 Zur Ausgabe

Update Onkologie

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