RNA binding protein LARP6 affects invasion and prognosis of gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HU Renwang ,  GONG Jianping

Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan 430000, P. R. China;

Corresponding author：

GONG Jianping, Email: jpgong@tjh.tjmu.edu.cn

Keywords：

gastric cancer; La-related protein 6; RNA binding protein; prognosis

DOI：

10.7507/1007-9424.202003058

Video：

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Objective To explore the effect of La-related protein 6 (LARP6) gene on the survival of postoperative patients with gastric cancer, and to explore its relationship with immune cell infiltration.Methods The clinical survival information and gene expression information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The relationship between LARP6 gene expression and clinical characteristics of patients were analyzed. Cox proportion hazard regression model was used to find out the prognostic risk factors of gastric cancer patients, and then Kaplan-Meier plotter database was used to verify. Then the correlation between LARP6 gene expression and immunity was proved by Tumor IMmune Estimation Resource (TIMER) immune database.Results In gastric cancer patients, the expression of LARP6 gene was related to pathological stage, T stage, and N stage (P<0.05), but not related to M stage and sex (P>0.05). Multivariate Cox proportion hazard regression analysis showed that age [HR=2.022, 95%CI was (1.287, 3.176), P=0.002] and LARP6 gene expression [HR=1.176, 95%CI was (1.070, 1.293), P<0.001] were prognostic factors. Further verified by Kaplan Meier plotter database, the results also showed that the overall survival (OS) and progression-free survival (PFS) of gastric cancer patients with high expression of LAPR6 gene were worse than those with low expression of LARP6 gene (P<0.001). TIMER database was used to explore the correlation between the expression level of LARP6 gene and immune cell infiltration in patients with gastric cancer, and the results showed that the expression level of LARP6 gene in gastric cancer patients was positively correlated with the infiltration number of CD4⁺ T cells and macrophage cell (P<0.001). Log-rank results showed that infiltration number of macrophage cell and LARP6 gene expression were risk factors for clinical prognosis of gastric cancer patients (P<0.05).Conclusions Macrophage cell andcell and LARP6 gene expression are risk factors for gastric cancer patients. LARP6 may be a new target for the treatment of gastric cancer.

Citation： HU Renwang, GONG Jianping. RNA binding protein LARP6 affects invasion and prognosis of gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(11): 1408-1412. doi: 10.7507/1007-9424.202003058 Copy

1.	Maraia RJ, Mattijssen S, Cruz-Gallardo I, et al. The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives. Wiley Interdiscip Rev RNA, 2017, 8(6): 10.1002/wrna.1430.
2.	Wolin SL, Cedervall T. The La protein. Annu Rev Biochem, 2002, 71: 375-403.
3.	Sommer G, Dittmann J, Kuehnert J, et al. The RNA-binding protein La contributes to cell proliferation and CCND1 expression. Oncogene, 2011, 30(4): 434-444.
4.	Tang J, Zhang ZH, Liu GL. A systematic analysis of the predicted human La protein targets identified a hepatitis B virus infection signature. J Viral Hepat, 2013, 20(1): 12-23.
5.	Tang J, Huang ZM, Chen YY, et al. A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation. PLoS One, 2012, 7(4): e36363.
6.	Tong S, Pan J, Tang J. Study on the structure optimization and anti-hepatitis B virus activity of novel human La protein inhibitor HBSC11. J Med Virol, 2019, 91(10): 1818-1829.
7.	Stavraka C, Blagden S. The La-related proteins, a family with connections to cancer. Biomolecules, 2015, 5(4): 2701-2722.
8.	Mura M, Hopkins TG, Michael T, et al. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene, 2015, 34(39): 5025-5036.
9.	Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumorinfil-trating immune cells. Nucleic Acids Res, 2020, 48(W1): W509-W514.
10.	Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res, 2017, 77(21): e108-e110.
11.	Li B, Severson E, Pignon JC, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol, 2016, 17(1): 174.
12.	Kechavarzi B, Janga SC. Dissecting the expression landscape of RNA-binding proteins in human cancers. Genome Biol, 2014, 15(1): R14.
13.	Castello A, Fischer B, Eichelbaum K, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell, 2012, 149(6): 1393-1406.
14.	陈昆仑, 吴怡, 李牧, 等. RNA 结合蛋白 La 在宫颈癌组织中的表达及临床意义. 南方医科大学学报杂志, 2013, 33(7): 999-1003.
15.	Egiz M, Usui T, Ishibashi M, et al. La-related protein 4 as a suppressor for motility of ovarian cancer cells. Tohoku J Exp Med, 2019, 247(1): 59-67.
16.	Kato M, Goto Y, Matsushita R, 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): 710-718.
17.	Xu Z, Xu J, Lu H, et al. LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma. Oncol Rep, 2017, 38(6): 3659-3667.
18.	Koso H, Yi H, Sheridan P, et al. Identification of RNA-binding protein LARP4B as a tumor suppressor in glioma. Cancer Res, 2016, 76(8): 2254-2264.
19.	Ji X, Lu H, Zhou Q, et al. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. Elife, 2014, 3: e02907.
20.	Sommer G, Rossa C, Chi AC, et al. Implication of RNA-binding protein La in proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. PLoS One, 2011, 6(10): e25402.
21.	Xie C, Huang L, Xie S, et al. LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma. J Transl Med, 2013, 11: 272.
22.	Ye L, Lin ST, Mi YS, et al. Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target. Tumour Biol, 2016, 37(11): 14585-14594.
23.	黄理宾, 陈海宁, 杨廷翰, 等. 胃癌的免疫治疗. 中国普外基础与临床杂志, 2019, 26(7): 779-784.
24.	Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141(1): 39-51.
25.	De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell, 2013, 23(3): 277-286.
26.	Cianciaruso C, Beltraminelli T, Duval F, et al. Molecular profiling and functional analysis of macrophage-derived tumor extracellular vesicles. Cell Rep, 2019, 27(10): 3062-3080.
27.	Al-Ejeh F, Darby JM, Brown MP. The La autoantigen is a malignancy-associated cell death target that is induced by DNA-damaging drugs. Clin Cancer Res, 2007, 13(18 Pt 2): 5509s-5518s.

1. Maraia RJ, Mattijssen S, Cruz-Gallardo I, et al. The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives. Wiley Interdiscip Rev RNA, 2017, 8(6): 10.1002/wrna.1430.
2. Wolin SL, Cedervall T. The La protein. Annu Rev Biochem, 2002, 71: 375-403.
3. Sommer G, Dittmann J, Kuehnert J, et al. The RNA-binding protein La contributes to cell proliferation and CCND1 expression. Oncogene, 2011, 30(4): 434-444.
4. Tang J, Zhang ZH, Liu GL. A systematic analysis of the predicted human La protein targets identified a hepatitis B virus infection signature. J Viral Hepat, 2013, 20(1): 12-23.
5. Tang J, Huang ZM, Chen YY, et al. A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation. PLoS One, 2012, 7(4): e36363.
6. Tong S, Pan J, Tang J. Study on the structure optimization and anti-hepatitis B virus activity of novel human La protein inhibitor HBSC11. J Med Virol, 2019, 91(10): 1818-1829.
7. Stavraka C, Blagden S. The La-related proteins, a family with connections to cancer. Biomolecules, 2015, 5(4): 2701-2722.
8. Mura M, Hopkins TG, Michael T, et al. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene, 2015, 34(39): 5025-5036.
9. Li T, Fu J, Zeng Z, et al. TIMER2.0 for analysis of tumorinfil-trating immune cells. Nucleic Acids Res, 2020, 48(W1): W509-W514.
10. Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res, 2017, 77(21): e108-e110.
11. Li B, Severson E, Pignon JC, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol, 2016, 17(1): 174.
12. Kechavarzi B, Janga SC. Dissecting the expression landscape of RNA-binding proteins in human cancers. Genome Biol, 2014, 15(1): R14.
13. Castello A, Fischer B, Eichelbaum K, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell, 2012, 149(6): 1393-1406.
14. 陈昆仑, 吴怡, 李牧, 等. RNA 结合蛋白 La 在宫颈癌组织中的表达及临床意义. 南方医科大学学报杂志, 2013, 33(7): 999-1003.
15. Egiz M, Usui T, Ishibashi M, et al. La-related protein 4 as a suppressor for motility of ovarian cancer cells. Tohoku J Exp Med, 2019, 247(1): 59-67.
16. Kato M, Goto Y, Matsushita R, 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): 710-718.
17. Xu Z, Xu J, Lu H, et al. LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma. Oncol Rep, 2017, 38(6): 3659-3667.
18. Koso H, Yi H, Sheridan P, et al. Identification of RNA-binding protein LARP4B as a tumor suppressor in glioma. Cancer Res, 2016, 76(8): 2254-2264.
19. Ji X, Lu H, Zhou Q, et al. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. Elife, 2014, 3: e02907.
20. Sommer G, Rossa C, Chi AC, et al. Implication of RNA-binding protein La in proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. PLoS One, 2011, 6(10): e25402.
21. Xie C, Huang L, Xie S, et al. LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma. J Transl Med, 2013, 11: 272.
22. Ye L, Lin ST, Mi YS, et al. Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target. Tumour Biol, 2016, 37(11): 14585-14594.
23. 黄理宾, 陈海宁, 杨廷翰, 等. 胃癌的免疫治疗. 中国普外基础与临床杂志, 2019, 26(7): 779-784.
24. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141(1): 39-51.
25. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell, 2013, 23(3): 277-286.
26. Cianciaruso C, Beltraminelli T, Duval F, et al. Molecular profiling and functional analysis of macrophage-derived tumor extracellular vesicles. Cell Rep, 2019, 27(10): 3062-3080.
27. Al-Ejeh F, Darby JM, Brown MP. The La autoantigen is a malignancy-associated cell death target that is induced by DNA-damaging drugs. Clin Cancer Res, 2007, 13(18 Pt 2): 5509s-5518s.

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RNA binding protein LARP6 affects invasion and prognosis of gastric cancer

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