Effect of DDX46 gene on the growth of xenografted tumor of esophageal squamous cell carcinoma in nude mice_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 LI Bin , SONG Tieniu , JIANG Peng , YANG Jianbao , ZHU Duojie , LIN Junping , Feng Haiming , JING Tao

Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou, 730030, P.R.China;

Corresponding author：

LI Bin, Email: dr.leebin@outlook.com

Keywords：

Esophageal squamous cell carcinoma; DDX46; xenografted tumor; apoptosis; in vivo influorescence imaging

DOI：

10.7507/1007-4848.201807008

Video：

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Objective To observe the growth of xenografted tumor in nude mice after DDX46 expression decreased, and to further study the role of DDX46 in the development and progression of esophageal squamous cell carcinoma. Methods DDX46-shRNA mediated RNAi was applied to silencing DDX46 in Eca-109 cells. Twenty-five female BALB/c nude mice were divided into 3 groups: an experiment group (DDX46-shRNA-LV, n=10), a control group (Control-LV, n=10) and a blank control group (Het-1A, n=5). The prepared Eca-109 cells of DDX46-shRNA-LV and Control-LV were subcutaneously injected into the right armpit of mice (4×10⁶ cells per mouse), while Het-1A cells were subcutaneously injected into the bilateral armpits of mice (4×10⁶ cells per side). Tumor growth was monitored twice a week on the 14th day after injection. Tumor volume was measured with calipers, in vivo imager to observe the fluorescence of each group. Further, western blotting analysis was used to detect the changes of apoptosis signaling molecules in xenografted tumor after DDX46 silence. Results The growth of xenografted tumor in nude mice was significantly slower in the DDX46-shRNA-LV group than that in the Control-LV group throughout the study period (P<0.001). Western blotting analysis showed that silencing DDX46 effectively suppressed the expression of DDX46, and upregulated the expression of cleaved Caspase-3 and cleaved PARP-1 in xenografted tumor (P<0.01). Conclusion DDX46 is involved in the development and progression of esophageal squamous cell carcinoma, and the silence of DDX46 expression can inhibit the growth of esophageal squamous cell carcinoma, which probably by positive regulation of apoptosis signaling pathway.

Citation： LI Bin, SONG Tieniu, JIANG Peng, YANG Jianbao, ZHU Duojie, LIN Junping, Feng Haiming, JING Tao. Effect of DDX46 gene on the growth of xenografted tumor of esophageal squamous cell carcinoma in nude mice. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(2): 169-174. doi: 10.7507/1007-4848.201807008 Copy

1.	Lee AS, Kranzusch PJ, Doudna JA, et al. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature, 2016, 536(7614): 96-99.
2.	Kosowski TR, Keys HR, Quan TK, et al. DExD/H-box Prp5 protein is in the spliceosome during most of the splicing cycle. RNA, 2009, 15(7): 1345-1362.
3.	Liang WW, Cheng SC. A novel mechanism for Prp5 function in prespliceosome formation and proofreading the branch site sequence. Genes Dev, 2015, 29(1): 81-93.
4.	Li M, Ma YC, Huang P, et al. Lentiviral DDX46 knockdown inhibits growth and induces apoptosis in human colorectal cancer cells. Gene, 2015, 560(2): 237-244.
5.	Jiang F, Zhang D, Li G, et al. Knockdown of DDX46 inhibits the invasion and tumorigenesis in osteosarcoma cells. Oncol Res, 2017, 25(3): 417-425.
6.	刘熹, 张冲, 黄邓高, 等. DDX46 基因慢病毒载体的构建及其在人膀胱癌细胞中的表达. 安徽医学, 2018, 39(1): 1-5.
7.	Li B, Li YM, He WT, et al. Knockdown of DDX46 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma cells. Oncol Rep, 2016, 36(1): 223-230.
8.	高华, 宋铁牛, 李斌, 等. 解旋酶 DDX46 基因对食管鳞癌 Eca-109 细胞增殖及凋亡的影响. 癌变·畸变·突变, 2017, 29(3): 216-221, 229.
9.	Zielske SP, Stevenson M. Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian immunodeficiency virus infection of primary macrophages. J Virol, 2005, 79(17): 11541-11546.
10.	Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
11.	Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14(CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
12.	Smyth EC, Lagergren J, Fitzgerald RC, et al. Oesophageal cancer. Nat Rev Dis Primers, 2017, 3: 17048.
13.	Linder P, Fuller-Pace FV. Looking back on the birth of DEAD-box RNA helicases. Biochim Biophys Acta, 2013, 1829(8): 750-755.
14.	Owttrim GW. RNA helicases: diverse roles in prokaryotic response to abiotic stress. RNA Biol, 2013, 10(1): 96-110.
15.	Heerma van Voss MR, van Diest PJ, Raman V. Targeting RNA helicases in cancer: the translation trap. Biochim Biophys Acta, 2017, 1868(2): 510-520.
16.	Abdelhaleem M, Maltais L, Wain H. The human DDX and DHX gene families of putative RNA helicases. Genomics, 2003, 81(6): 618-622.
17.	Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 1999, 6(2): 99-104.
18.	Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. J Clin Invest, 2005, 115(10): 2665-2672.
19.	Zhang C, Kuang M, Li M, et al. SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression. Sci Rep, 2016, 6: 34508.
20.	Zheng Q, Hou J, Zhou Y, et al. The RNA helicase DDX46 inhibits innate immunity by entrapping m⁶A-demethylated antiviral transcripts in the nucleus. Nat Immunol, 2017, 18(10): 1094-1103.

1. Lee AS, Kranzusch PJ, Doudna JA, et al. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature, 2016, 536(7614): 96-99.
2. Kosowski TR, Keys HR, Quan TK, et al. DExD/H-box Prp5 protein is in the spliceosome during most of the splicing cycle. RNA, 2009, 15(7): 1345-1362.
3. Liang WW, Cheng SC. A novel mechanism for Prp5 function in prespliceosome formation and proofreading the branch site sequence. Genes Dev, 2015, 29(1): 81-93.
4. Li M, Ma YC, Huang P, et al. Lentiviral DDX46 knockdown inhibits growth and induces apoptosis in human colorectal cancer cells. Gene, 2015, 560(2): 237-244.
5. Jiang F, Zhang D, Li G, et al. Knockdown of DDX46 inhibits the invasion and tumorigenesis in osteosarcoma cells. Oncol Res, 2017, 25(3): 417-425.
6. 刘熹, 张冲, 黄邓高, 等. DDX46 基因慢病毒载体的构建及其在人膀胱癌细胞中的表达. 安徽医学, 2018, 39(1): 1-5.
7. Li B, Li YM, He WT, et al. Knockdown of DDX46 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma cells. Oncol Rep, 2016, 36(1): 223-230.
8. 高华, 宋铁牛, 李斌, 等. 解旋酶 DDX46 基因对食管鳞癌 Eca-109 细胞增殖及凋亡的影响. 癌变·畸变·突变, 2017, 29(3): 216-221, 229.
9. Zielske SP, Stevenson M. Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian immunodeficiency virus infection of primary macrophages. J Virol, 2005, 79(17): 11541-11546.
10. Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
11. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14(CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125): 1023-1075.
12. Smyth EC, Lagergren J, Fitzgerald RC, et al. Oesophageal cancer. Nat Rev Dis Primers, 2017, 3: 17048.
13. Linder P, Fuller-Pace FV. Looking back on the birth of DEAD-box RNA helicases. Biochim Biophys Acta, 2013, 1829(8): 750-755.
14. Owttrim GW. RNA helicases: diverse roles in prokaryotic response to abiotic stress. RNA Biol, 2013, 10(1): 96-110.
15. Heerma van Voss MR, van Diest PJ, Raman V. Targeting RNA helicases in cancer: the translation trap. Biochim Biophys Acta, 2017, 1868(2): 510-520.
16. Abdelhaleem M, Maltais L, Wain H. The human DDX and DHX gene families of putative RNA helicases. Genomics, 2003, 81(6): 618-622.
17. Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 1999, 6(2): 99-104.
18. Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. J Clin Invest, 2005, 115(10): 2665-2672.
19. Zhang C, Kuang M, Li M, et al. SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression. Sci Rep, 2016, 6: 34508.
20. Zheng Q, Hou J, Zhou Y, et al. The RNA helicase DDX46 inhibits innate immunity by entrapping m⁶A-demethylated antiviral transcripts in the nucleus. Nat Immunol, 2017, 18(10): 1094-1103.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Effect of DDX46 gene on the growth of xenografted tumor of esophageal squamous cell carcinoma in nude mice

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