Study of influences of FOXA1 regulating Notch pathway on proliferation and invasion of colon cancer cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIU Kefeng , WANG Wei , FAN Yonggang , YU Yingjie

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471000, P. R. China;

Corresponding author：

LIU Kefeng, Email: lxf0705n@163.com

Keywords：

colon cancer; forkhead box protein A1; Notch pathway; proliferation; invasion

DOI：

10.7507/1007-9424.202105038

Video：

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Objective To investigate effect of Notch pathway regulating by inhibiting expression of forkhead box protein A1 (FOXA1) on proliferation and invasion of colon cancer SW480 cells. Methods The colon cancer tissues and their corresponding paracancerous tissues of 45 patients with colon cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from June 2019 to February 2021 were selected. The immunohistochemistry and real-time fluorescent quantitative PCR (qRT-PCR) methods were used to detect the expressions of FOXA1 protein and mRNA in the tissues, respectively. In addition, SW480 cells were divided into control group (untreated), shRNA-NC group (transfected with shRNA-NC), sh-FOXA1 group (transfected with sh-FOXA1), sh-FOXA1+sodium valproate group (Add 8 mmol/L Notch pathway activator sodium valproate after transfection with sh-FOXA1). Then the qRT-PCR, MTT, clone formation test, and Transwell methods were used to detect the expressions of FOXA1 mRNA, proliferation, clonogenic ability, invasion and migration of cells in each group. Western blot method was used to detect the proliferation (c-Myc, cyclinD1), invasion and migration [matrix metalloproteinase (MMP）9, MMP2], epithelial-mesenchymal transition (Vimentin, N-cadherin, E-cadherin) and Notch pathway (Notch-1, Hes-1) related protein expressions of cells in each group. Results ① In the clinical cases, the expression levels of FOXA1 protein and mRNA in the colon cancer tissues were higher than those in the corresponding paracancerous tissues (protein: 0.085±0.028 vs. 0.034±0.010, t=11.036, P<0.001; mRNA: 1.62±0.34 vs. 1.00±0.09, t=11.671, P<0.001). ② In the cell experiment, compared with the control group and shRNA-NC group, the cell survival rate, and numbers of cloned cells, invasion and migrating cells were significantly reduced (P<0.05), correspondingly, the related proteins expression levels of c-Myc, cyclinD1, MMP9, MMP2, Vimentin, N-cadherin, Notch-1, Hes-1 were significantly reduced (P<0.05) and the protein expression level of E-cadherin was significantly increased (P<0.05) in the sh-FOXA1 group, which were reversed after adding the Notch pathway activator sodium valproate (P<0.05). Conclusion FOXA1 highly expresses in colon cancer tissues and colon cancer cells and it might promote the proliferation, invasion and migration of SW480 cells by activating the Notch pathway.

Citation： LIU Kefeng, WANG Wei, FAN Yonggang, YU Yingjie. Study of influences of FOXA1 regulating Notch pathway on proliferation and invasion of colon cancer cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(4): 444-449. doi: 10.7507/1007-9424.202105038 Copy

1.	Huang C, Li R, Shi W, et al. Discovery of the anti-tumor mechanism of calycosin against colorectal cancer by using system pharmacology approach. Med Sci Monit, 2019, 25: 5589-5593.
2.	Cheng B, Rong A, Zhou Q, et al. LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway. J Exp Clin Cancer Res, 2020, 39(1): 5. doi: 10.1186/s13046-019-1510-7.
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4.	Lazar SB, Pongor L, Li XL, et al. Genome-wide analysis of the FOXA1 transcriptional network identifies novel protein-coding and long noncoding RNA targets in colorectal cancer cells. Mol Cell Biol, 2020, 40(21): e00224-20. doi: 10.1128/MCB.00224-20.
5.	Venkatesh V, Nataraj R, Thangaraj GS, et al. Targeting Notch signalling pathway of cancer stem cells. Stem Cell Investig, 2018, 5: 5. doi: 10.21037/sci.2018.02.02.
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7.	Qiu M, Bao W, Wang J, et al. FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer. BMC Cancer, 2014, 14: 78. doi: 10.1186/1471-2407-14-78.
8.	周跃. ECM 蛋白 SRPX2 对结肠癌 SW480 细胞生物学行为的影响. 兰州: 兰州大学, 2015.
9.	Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2017, 66(4): 683-691.
10.	Gupta R, Bhatt LK, Johnston TP, et al. Colon cancer stem cells: potential target for the treatment of colorectal cancer. Cancer Biol Ther, 2019, 20(8): 1068-1082.
11.	简小兰, 曾普华, 李勇敏, 等. 健脾消癌方对结肠癌细胞中 Akt/mTOR 信号通路的影响. 中国实验方剂学杂志, 2020, 26(7): 73-78.
12.	Zhou M, Liu X, Li Z, et al. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer, 2018, 143(4): 921-930.
13.	樊明湖, 陈保华, 车河, 等. miR-186 上调 Dicer1 抑制结肠癌细胞侵袭转移的分子机制. 现代免疫学, 2020, 40(3): 177-186.
14.	张殷, 肖毅. 结肠癌的新辅助治疗. 中国普外基础与临床杂志, 2020, 27(12): 1480-1484.
15.	瞿小祥, 鲁小红. 靶向抑制转录因子 FOXA1 对前列腺癌细胞增殖的影响及机制研究. 中国性科学, 2020, 29(5): 1-3.
16.	Parolia A, Cieslik M, Chu SC, et al. Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer. Nature, 2019, 571(7765): 413-418.
17.	王凡, 刘伟, 李强, 等. CDKN3 和 FOXA1 mRNA 在直肠癌中的表达关系及意义. 河北医学, 2021, 27(1): 84-89.
18.	冷冰洁, 姜晗, 杨小毅, 等. FOXA1 及 FOXD3 蛋白联合检测对胃癌临床诊断及患者生存率的意义. 现代消化及介入诊疗, 2020, 25(3): 367-369.
19.	邓振宇, 何传凤, 牛占杰. miR-760 在宫颈鳞状细胞癌组织和细胞中的表达及其对 SiHa 细胞恶性生物学行为的作用. 中国肿瘤生物治疗杂志, 2019, 26(10): 1120-1127.
20.	孟小琴, 李云峰, 周毅, 等. 过表达 OTUD1 对结肠癌细胞 HCT116 增殖和侵袭的影响及机制研究. 重庆医科大学学报, 2018, 43(5): 687-691.
21.	钱金锋, 杨其昌, 谢慧君, 等. 乳腺浸润性导管癌中上皮间质转化相关蛋白表达与临床病理特征和预后的关系. 中国普外基础与临床杂志, 2015, 22(5): 591-596.
22.	Tyagi A, Sharma AK, Damodaran C. A review on Notch signaling and colorectal cancer. Cells, 2020, 9(6): 1549. doi: 10.3390/cells9061549.
23.	Li L, Tang P, Li S, et al. Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy. Med Oncol, 2017, 34(10): 180. doi: 10.1007/s12032-017-1039-6.
24.	Rodrigues C, Joy LR, Sachithanandan SP, et al. Notch signalling in cervical cancer. Exp Cell Res, 2019, 385(2): 111682. doi: 10.1016/j.yexcr.2019.111682.
25.	Kontomanolis EN, Kalagasidou S, Pouliliou S, et al. The Notch pathway in breast cancer progression. Sci World J, 2018, 2018: 2415489. doi: 10.1155/2018/2415489.
26.	Vinson KE, George DC, Fender AW, et al. The Notch pathway in colorectal cancer. Int J Cancer, 2016, 138(8): 1835-1842.

1. Huang C, Li R, Shi W, et al. Discovery of the anti-tumor mechanism of calycosin against colorectal cancer by using system pharmacology approach. Med Sci Monit, 2019, 25: 5589-5593.
2. Cheng B, Rong A, Zhou Q, et al. LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway. J Exp Clin Cancer Res, 2020, 39(1): 5. doi: 10.1186/s13046-019-1510-7.
3. Pan J, Xu Z, Xu M, et al. Knockdown of forkhead box A1 suppresses the tumorigenesis and progression of human colon cancer cells through regulating the phosphatase and tensin homolog/Akt pathway. J Int Med Res, 2020, 48(12): 300060520971453. doi: 10.1177/0300060520971453.
4. Lazar SB, Pongor L, Li XL, et al. Genome-wide analysis of the FOXA1 transcriptional network identifies novel protein-coding and long noncoding RNA targets in colorectal cancer cells. Mol Cell Biol, 2020, 40(21): e00224-20. doi: 10.1128/MCB.00224-20.
5. Venkatesh V, Nataraj R, Thangaraj GS, et al. Targeting Notch signalling pathway of cancer stem cells. Stem Cell Investig, 2018, 5: 5. doi: 10.21037/sci.2018.02.02.
6. Malki A, ElRuz RA, Gupta I, et al. Molecular mechanisms of colon cancer progression and metastasis: Recent insights and advancements. Int J Mol Sci, 2020, 22(1): 130. doi: 10.3390/ijms22010130.
7. Qiu M, Bao W, Wang J, et al. FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer. BMC Cancer, 2014, 14: 78. doi: 10.1186/1471-2407-14-78.
8. 周跃. ECM 蛋白 SRPX2 对结肠癌 SW480 细胞生物学行为的影响. 兰州: 兰州大学, 2015.
9. Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2017, 66(4): 683-691.
10. Gupta R, Bhatt LK, Johnston TP, et al. Colon cancer stem cells: potential target for the treatment of colorectal cancer. Cancer Biol Ther, 2019, 20(8): 1068-1082.
11. 简小兰, 曾普华, 李勇敏, 等. 健脾消癌方对结肠癌细胞中 Akt/mTOR 信号通路的影响. 中国实验方剂学杂志, 2020, 26(7): 73-78.
12. Zhou M, Liu X, Li Z, et al. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer, 2018, 143(4): 921-930.
13. 樊明湖, 陈保华, 车河, 等. miR-186 上调 Dicer1 抑制结肠癌细胞侵袭转移的分子机制. 现代免疫学, 2020, 40(3): 177-186.
14. 张殷, 肖毅. 结肠癌的新辅助治疗. 中国普外基础与临床杂志, 2020, 27(12): 1480-1484.
15. 瞿小祥, 鲁小红. 靶向抑制转录因子 FOXA1 对前列腺癌细胞增殖的影响及机制研究. 中国性科学, 2020, 29(5): 1-3.
16. Parolia A, Cieslik M, Chu SC, et al. Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer. Nature, 2019, 571(7765): 413-418.
17. 王凡, 刘伟, 李强, 等. CDKN3 和 FOXA1 mRNA 在直肠癌中的表达关系及意义. 河北医学, 2021, 27(1): 84-89.
18. 冷冰洁, 姜晗, 杨小毅, 等. FOXA1 及 FOXD3 蛋白联合检测对胃癌临床诊断及患者生存率的意义. 现代消化及介入诊疗, 2020, 25(3): 367-369.
19. 邓振宇, 何传凤, 牛占杰. miR-760 在宫颈鳞状细胞癌组织和细胞中的表达及其对 SiHa 细胞恶性生物学行为的作用. 中国肿瘤生物治疗杂志, 2019, 26(10): 1120-1127.
20. 孟小琴, 李云峰, 周毅, 等. 过表达 OTUD1 对结肠癌细胞 HCT116 增殖和侵袭的影响及机制研究. 重庆医科大学学报, 2018, 43(5): 687-691.
21. 钱金锋, 杨其昌, 谢慧君, 等. 乳腺浸润性导管癌中上皮间质转化相关蛋白表达与临床病理特征和预后的关系. 中国普外基础与临床杂志, 2015, 22(5): 591-596.
22. Tyagi A, Sharma AK, Damodaran C. A review on Notch signaling and colorectal cancer. Cells, 2020, 9(6): 1549. doi: 10.3390/cells9061549.
23. Li L, Tang P, Li S, et al. Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy. Med Oncol, 2017, 34(10): 180. doi: 10.1007/s12032-017-1039-6.
24. Rodrigues C, Joy LR, Sachithanandan SP, et al. Notch signalling in cervical cancer. Exp Cell Res, 2019, 385(2): 111682. doi: 10.1016/j.yexcr.2019.111682.
25. Kontomanolis EN, Kalagasidou S, Pouliliou S, et al. The Notch pathway in breast cancer progression. Sci World J, 2018, 2018: 2415489. doi: 10.1155/2018/2415489.
26. Vinson KE, George DC, Fender AW, et al. The Notch pathway in colorectal cancer. Int J Cancer, 2016, 138(8): 1835-1842.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of influences of FOXA1 regulating Notch pathway on proliferation and invasion of colon cancer cells

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