Effect of eIF6 gene expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHONG Yonghui ¹ , XIE Fuchuan ² , WEI Yisheng ³ , HUANG Xuejun ¹

1. Department of General Surgery, Huizhou Central People’s Hospital, Huizhou, Guangdong 516001, P. R. China;
2. Department of Tumor Radiotherapy, Huizhou Central People’s Hospital, Huizhou, Guangdong 516001, P. R. China;
3. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P. R. China;

Corresponding author：

ZHONG Yonghui, Email: zyf1983404@163.com

Keywords：

eukaryotic initiation factor 6; colorectal cancer; invasion and metastasis; Wnt/β-catenin pathway; epithelial mesenchymal transition

DOI：

10.7507/1007-9424.202012136

Video：

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Objective To investigate the effect of eukaryotic initiation factor 6 (eIF6) expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway.Methods Immunohistochemistry was used to detect the expressions of eIF6 protein in colorectal cancer tissues and paracancerous tissue. Sw837 cell lines with overexpression/knockdown eIF6 were constructed by transfection and divided into control group, empty plasmid group, overexpression group and knockdown group respectively. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blotting (WB) were used to verify the overexpression/knockdown of eIF6 in sw837 cells. WB was used to detect the expressions of β-catenin, glycogen synthase kinase-3β (GSK-3β), anaphase promoting complex (APC), zinc finger transcription factor SNAI (Snail), E-cadherin and Vimentin. Transwell invasion test, Scratch test and subcutaneous tumorigenesis test were used to detect the migration ability, invasion ability and tumorigenesis ability in vivo of cells. The pathological changes of the transplanted tumor were observed by HE staining.Results The positive expression rate of eIF6 protein in cancer tissues was significantly higher than that in adjacent tissues (P<0.05). Compared with those in the control group, the protein expression levels of β-catenin, Snail and Vimentin in the overexpression group were higher, the protein levels of GSK-3β, APC and E-cadherin were lower, the ability of cell migration and invasion, and tumorigenicity in vivo were enhanced, the difference were statistically significant (P<0.05). The protein expression levels of β-catenin, Snail and Vimentin were lower in knockdown group, the protein levels of GSK-3β, APC and E-cadherin were higher, the ability of cell migration and invasion, and tumorigenicity in vivo were reduced, the difference were statistically significant (P<0.05).Conclusion eIF6 may promote the invasion and metastasis of colorectal cancer cells by activating Wnt/β-catenin signaling pathway.

Citation： ZHONG Yonghui, XIE Fuchuan, WEI Yisheng, HUANG Xuejun. Effect of eIF6 gene expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(9): 1148-1154. doi: 10.7507/1007-9424.202012136 Copy

1.	Russo A, Gatti G, Alfieri R, et al. Modulating eIF6 levels unveils the role of translation in ecdysone biosynthesis during Drosophila development. Dev Biol, 2019, 455(1): 100-111.
2.	De Marco N, Tussellino M, Carotenuto R, et al. Eukaryotic initiation factor eIF6 modulates the expression of Kermit 2/XGIPC in IGF- regulated eye development. Dev Biol, 2017, 427(1): 148-154.
3.	Lin J, Yu X, Xie L, et al. eIF6 promotes colorectal cancer proliferation and invasion by regulating AKT-related signaling pathways. J Biomed Nanotechnol, 2019, 15(7): 1556-1567.
4.	Bai YQ, Feng JK, Zhang QF, et al. Effects of the eukaryotic initiation factor 6 gene on expression levels of inflammatory mediators in M2 macrophages during scar repair. Mol Med Rep, 2016, 14(1): 819-824.
5.	Gantenbein N, Bernhart E, Anders I, et al. Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression. Eur J Cancer, 2018, 101: 165-180.
6.	Golob-Schwarzl N, Wodlej C, Kleinegger F, et al. Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer. J Cancer Res Clin Oncol, 2019, 145(11): 2699-2711.
7.	Wu F, Xing T, Gao X, et al. miR-501-3p promotes colorectal cancer progression via activation of Wnt/β-catenin signaling. Int J Oncol, 2019, 55(3): 671-683.
8.	Zhang QW, Zhang XT, Tang CT, et al. EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β-catenin pathway. Mol Carcinog, 2019, 58(6): 967-979.
9.	Song W, Ma J, Lei B, et al. Sine oculis homeobox 1 promotes proliferation and migration of human colorectal cancer cells through activation of Wnt/β-catenin signaling. Cancer Sci, 2019, 110(2): 608-616.
10.	Zhu L, Yang N, Du G, et al. LncRNA CRNDE promotes the epithelial-mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/β-catenin signaling pathway. J Cell Biochem, 2018, 120(2): 1156-1164.
11.	He Y, Davies CM, Harrington BS, et al. CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin. Oncogene, 2020, 39(1): 219-233.
12.	Pyo MC, Chae SA, Yoo HJ, et al. Ochratoxin A induces epithelial-to-mesenchymal transition and renal fibrosis through TGF-β/Smad2/3 and Wnt1/β-catenin signaling pathways in vitro and in vivo. Arch Toxicol, 2020, 94(9): 3329-3342.
13.	Hu W, Li X, Cheng R, et al. NAV2 facilitates invasion of cutaneous melanoma cells by targeting SNAI2 through the GSK-3β/β-catenin pathway. Arch Dermatol Res, 2019, 311(5): 399-410.
14.	Kobayashi PE, Fonseca-Alves CE, Rivera-Calderón LG, et al. Deregulation of E-cadherin, β-catenin, APC and Caveolin-1 expression occurs in canine prostate cancer and metastatic processes. Res Vet Sci, 2018, 118: 254-261.
15.	Qiao Y, Wang J, Karagoz E, et al. Axis inhibition protein 1 (Axin1) deletion-induced hepatocarcinogenesis requires intact β-catenin but not notch cascade in mice. Hepatology, 2019, 70(6): 2003-2017.
16.	Zhao YR, Wang JL, Xu C, et al. HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling. Clin Sci (Lond), 2019, 133(14): 1645-1662.
17.	Zhou P, Li Y, Li B, et al. NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer. Oncogene, 2019, 38(27): 5500-5515.
18.	Zhang L, Yao HR, Liu SK, et al. Long noncoding RNA ROR1-AS1 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in cervical cancer. Eur Rev Med Pharmacol Sci, 2020, 24(6): 2928-2937.
19.	Li S, Han Z, Zhao N, et al. Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway. Cell Signal, 2018, 47: 79-87.
20.	Chen JS, Huang JQ, Luo B, et al. PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer. Cancer Sci, 2019, 110(3): 997-1011.
21.	Wei Y, Zhang F, Zhang T, et al. LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer. Aging (Albany NY), 2019, 11(20): 8951-8968.
22.	Guo J, Zhang T, Dou D. Knockdown of HOXB8 inhibits tumor growth and metastasis by the inactivation of Wnt/β-catenin signaling pathway in osteosarcoma. Eur J Pharmacol, 2019, 854: 22-27.
23.	Gu J, Cui CF, Yang L, et al. Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial-mesenchymal transition via the Wnt/β-catenin pathway. Oncol Res, 2019, 27(2): 193-202.
24.	Wu L, Zhou Z, Han S, et al. PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1. Br J Cancer, 2020, 122(4): 578-589.

1. Russo A, Gatti G, Alfieri R, et al. Modulating eIF6 levels unveils the role of translation in ecdysone biosynthesis during Drosophila development. Dev Biol, 2019, 455(1): 100-111.
2. De Marco N, Tussellino M, Carotenuto R, et al. Eukaryotic initiation factor eIF6 modulates the expression of Kermit 2/XGIPC in IGF- regulated eye development. Dev Biol, 2017, 427(1): 148-154.
3. Lin J, Yu X, Xie L, et al. eIF6 promotes colorectal cancer proliferation and invasion by regulating AKT-related signaling pathways. J Biomed Nanotechnol, 2019, 15(7): 1556-1567.
4. Bai YQ, Feng JK, Zhang QF, et al. Effects of the eukaryotic initiation factor 6 gene on expression levels of inflammatory mediators in M2 macrophages during scar repair. Mol Med Rep, 2016, 14(1): 819-824.
5. Gantenbein N, Bernhart E, Anders I, et al. Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression. Eur J Cancer, 2018, 101: 165-180.
6. Golob-Schwarzl N, Wodlej C, Kleinegger F, et al. Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer. J Cancer Res Clin Oncol, 2019, 145(11): 2699-2711.
7. Wu F, Xing T, Gao X, et al. miR-501-3p promotes colorectal cancer progression via activation of Wnt/β-catenin signaling. Int J Oncol, 2019, 55(3): 671-683.
8. Zhang QW, Zhang XT, Tang CT, et al. EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β-catenin pathway. Mol Carcinog, 2019, 58(6): 967-979.
9. Song W, Ma J, Lei B, et al. Sine oculis homeobox 1 promotes proliferation and migration of human colorectal cancer cells through activation of Wnt/β-catenin signaling. Cancer Sci, 2019, 110(2): 608-616.
10. Zhu L, Yang N, Du G, et al. LncRNA CRNDE promotes the epithelial-mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/β-catenin signaling pathway. J Cell Biochem, 2018, 120(2): 1156-1164.
11. He Y, Davies CM, Harrington BS, et al. CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin. Oncogene, 2020, 39(1): 219-233.
12. Pyo MC, Chae SA, Yoo HJ, et al. Ochratoxin A induces epithelial-to-mesenchymal transition and renal fibrosis through TGF-β/Smad2/3 and Wnt1/β-catenin signaling pathways in vitro and in vivo. Arch Toxicol, 2020, 94(9): 3329-3342.
13. Hu W, Li X, Cheng R, et al. NAV2 facilitates invasion of cutaneous melanoma cells by targeting SNAI2 through the GSK-3β/β-catenin pathway. Arch Dermatol Res, 2019, 311(5): 399-410.
14. Kobayashi PE, Fonseca-Alves CE, Rivera-Calderón LG, et al. Deregulation of E-cadherin, β-catenin, APC and Caveolin-1 expression occurs in canine prostate cancer and metastatic processes. Res Vet Sci, 2018, 118: 254-261.
15. Qiao Y, Wang J, Karagoz E, et al. Axis inhibition protein 1 (Axin1) deletion-induced hepatocarcinogenesis requires intact β-catenin but not notch cascade in mice. Hepatology, 2019, 70(6): 2003-2017.
16. Zhao YR, Wang JL, Xu C, et al. HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling. Clin Sci (Lond), 2019, 133(14): 1645-1662.
17. Zhou P, Li Y, Li B, et al. NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer. Oncogene, 2019, 38(27): 5500-5515.
18. Zhang L, Yao HR, Liu SK, et al. Long noncoding RNA ROR1-AS1 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in cervical cancer. Eur Rev Med Pharmacol Sci, 2020, 24(6): 2928-2937.
19. Li S, Han Z, Zhao N, et al. Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway. Cell Signal, 2018, 47: 79-87.
20. Chen JS, Huang JQ, Luo B, et al. PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer. Cancer Sci, 2019, 110(3): 997-1011.
21. Wei Y, Zhang F, Zhang T, et al. LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer. Aging (Albany NY), 2019, 11(20): 8951-8968.
22. Guo J, Zhang T, Dou D. Knockdown of HOXB8 inhibits tumor growth and metastasis by the inactivation of Wnt/β-catenin signaling pathway in osteosarcoma. Eur J Pharmacol, 2019, 854: 22-27.
23. Gu J, Cui CF, Yang L, et al. Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial-mesenchymal transition via the Wnt/β-catenin pathway. Oncol Res, 2019, 27(2): 193-202.
24. Wu L, Zhou Z, Han S, et al. PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1. Br J Cancer, 2020, 122(4): 578-589.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of eIF6 gene expression on invasion and metastasis of colorectal cancer cells and Wnt/β-catenin signaling pathway

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