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Published in: Tumor Biology 11/2016

Open Access 01-11-2016 | Original Article

Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target

Authors: Ling Ye, Sheng-tao Lin, Yu-shuai Mi, Yuan Liu, Yang Ma, Hui-min Sun, Zhi-hai Peng, Jun-wei Fan

Published in: Tumor Biology | Issue 11/2016

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Abstract

This study investigated the significance of La-related protein 1 (LARP1) in the development and progression of colorectal cancer (CRC). Quantitative real-time polymerase chain reaction and Western blot analyses were carried out to determine the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent normal mucosa. The expression of LARP1 was upregulated in CRC. Immunohistochemical analysis using tissue microarray was performed. A positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed using the Spearman’s correlation coefficient test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001), American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank (P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed that LARP1 was an independent prognostic factor for overall survival (OS; hazard rate (HR) = 0.244; 95 % confidence interval (CI), 0.078–0.769; P = 0.016) and disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086–0.917; P = 0.035) in CRC patients. LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.
Literature
1.
4.
go back to reference Prenen H, Vecchione L, Van Cutsem E. Role of targeted agents in metastatic colorectal cancer. Target Oncol. 2013;8(2):83–96.CrossRefPubMed Prenen H, Vecchione L, Van Cutsem E. Role of targeted agents in metastatic colorectal cancer. Target Oncol. 2013;8(2):83–96.CrossRefPubMed
6.
go back to reference Akkad J, Bochum S, Martens UM. Personalized treatment for colorectal cancer: novel developments and putative therapeutic strategies. Langenbeck’s Arch Surg. 2015;400(2):129–43.CrossRef Akkad J, Bochum S, Martens UM. Personalized treatment for colorectal cancer: novel developments and putative therapeutic strategies. Langenbeck’s Arch Surg. 2015;400(2):129–43.CrossRef
7.
go back to reference Fan J et al. Gene-expression profiling in Chinese patients with colon cancer by coupling experimental and bioinformatic genome wide gene-expression analyses: identification and validation of IFITM3 as a biomarker of early colon carcinogenesis. Cancer. 2008;113(2):266–75.CrossRefPubMed Fan J et al. Gene-expression profiling in Chinese patients with colon cancer by coupling experimental and bioinformatic genome wide gene-expression analyses: identification and validation of IFITM3 as a biomarker of early colon carcinogenesis. Cancer. 2008;113(2):266–75.CrossRefPubMed
10.
go back to reference Liu D et al. Activation of mammalian target of rapamycin pathway confers adverse outcome in non small cell lung carcinoma. Cancer. 2011;117(16):3763–73.CrossRefPubMed Liu D et al. Activation of mammalian target of rapamycin pathway confers adverse outcome in non small cell lung carcinoma. Cancer. 2011;117(16):3763–73.CrossRefPubMed
12.
go back to reference Lee HW, Lee EH, et al. Prognostic significance of phosphorylated 4E-binding protein 1 in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8(4):3955–62. Lee HW, Lee EH, et al. Prognostic significance of phosphorylated 4E-binding protein 1 in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8(4):3955–62.
13.
go back to reference Castello A et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell. 2012;149(6):1393–406.CrossRefPubMed Castello A et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell. 2012;149(6):1393–406.CrossRefPubMed
14.
go back to reference Mura M et al. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene. 2015;34(39):5025–36.CrossRefPubMed Mura M et al. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene. 2015;34(39):5025–36.CrossRefPubMed
15.
go back to reference Deragon J-M, Bousquet-Antonelli C. The role of LARP1 in translation and beyond. Wiley Interdisciplinary Reviews: RNA. 2015;6(4):399–417. Deragon J-M, Bousquet-Antonelli C. The role of LARP1 in translation and beyond. Wiley Interdisciplinary Reviews: RNA. 2015;6(4):399–417.
16.
17.
go back to reference Aoki K et al. LARP1 specifically recognizes the 3′ terminus of poly(a) mRNA. FEBS Lett. 2013;587(14):2173–8.CrossRefPubMed Aoki K et al. LARP1 specifically recognizes the 3′ terminus of poly(a) mRNA. FEBS Lett. 2013;587(14):2173–8.CrossRefPubMed
19.
go back to reference Tcherkezian J et al. Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5’TOP mRNA translation. Genes Dev. 2014;28(4):357–71.CrossRefPubMedPubMedCentral Tcherkezian J et al. Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5’TOP mRNA translation. Genes Dev. 2014;28(4):357–71.CrossRefPubMedPubMedCentral
20.
go back to reference Elias JM. Cell proliferation indexed a biomarker in solid tumors. Biotechnic & Histochemistry. 1996;72(2):78–85.CrossRef Elias JM. Cell proliferation indexed a biomarker in solid tumors. Biotechnic & Histochemistry. 1996;72(2):78–85.CrossRef
21.
go back to reference Guzinska-Ustymowicz K et al. Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res. 2009;29:3049–52. Guzinska-Ustymowicz K et al. Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res. 2009;29:3049–52.
22.
go back to reference Stoimenov I, Helleday T. PCNA on the crossroad of cancer. Biochem Soc Trans. 2009;37(Pt 3):605–13.CrossRefPubMed Stoimenov I, Helleday T. PCNA on the crossroad of cancer. Biochem Soc Trans. 2009;37(Pt 3):605–13.CrossRefPubMed
23.
go back to reference Zhang Z et al. Structure of monoubiquitinated PCNA: implications for DNA polymerase switching and Okazaki fragment maturation. Cell Cycle. 2012;11(11):2128–36.CrossRefPubMedPubMedCentral Zhang Z et al. Structure of monoubiquitinated PCNA: implications for DNA polymerase switching and Okazaki fragment maturation. Cell Cycle. 2012;11(11):2128–36.CrossRefPubMedPubMedCentral
24.
go back to reference Sophie Chauvet CM-Z et al. dlarp a new candidate Hox target in drosophila whose orthologue in mouse is expressed at sites of epithelium mesenchymal interactions. Dev Dyn. 2000;218:401–13.CrossRef Sophie Chauvet CM-Z et al. dlarp a new candidate Hox target in drosophila whose orthologue in mouse is expressed at sites of epithelium mesenchymal interactions. Dev Dyn. 2000;218:401–13.CrossRef
25.
go back to reference Ichihara K, Shimizu H, Taguchi O, et al. A Drosophila orthologue of larp protein family is required for multiple processes in male meiosis. Cell Struct Funct. 2007;32:89–100.CrossRefPubMed Ichihara K, Shimizu H, Taguchi O, et al. A Drosophila orthologue of larp protein family is required for multiple processes in male meiosis. Cell Struct Funct. 2007;32:89–100.CrossRefPubMed
26.
go back to reference Blagden SP et al. Drosophila LARP associates with poly(a)-binding protein and is required for male fertility and syncytial embryo development. Dev Biol. 2009;334(1):186–97.CrossRefPubMed Blagden SP et al. Drosophila LARP associates with poly(a)-binding protein and is required for male fertility and syncytial embryo development. Dev Biol. 2009;334(1):186–97.CrossRefPubMed
27.
28.
go back to reference Kato M et al. MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer. Int J Oncol. 2015;47(2):710–8.PubMed Kato M et al. MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer. Int J Oncol. 2015;47(2):710–8.PubMed
29.
go back to reference Kato K et al. Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: correlation with clinicopathological features and prognosis. J Oral Pathol Med. 2011;40(9):693–8.CrossRefPubMed Kato K et al. Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: correlation with clinicopathological features and prognosis. J Oral Pathol Med. 2011;40(9):693–8.CrossRefPubMed
30.
go back to reference Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122(20):3589–94. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122(20):3589–94.
Metadata
Title
Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target
Authors
Ling Ye
Sheng-tao Lin
Yu-shuai Mi
Yuan Liu
Yang Ma
Hui-min Sun
Zhi-hai Peng
Jun-wei Fan
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5332-3

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