[1]张博汝,魏柏,石晓雅,等.生物钟基因Bmal1对结肠癌细胞增殖的影响[J].新乡医学院学报,2022,39(11):1001-1005.[doi:10.7683/xxyxyxb.2022.11.001]
 ZHANG Boru,WEI Bai,SHI Xiaoya,et al.Effect of circadian clock gene Bmal1 on the proliferation of colon cancer cell[J].Journal of Xinxiang Medical University,2022,39(11):1001-1005.[doi:10.7683/xxyxyxb.2022.11.001]
点击复制

生物钟基因Bmal1对结肠癌细胞增殖的影响
分享到:

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年11
页码:
1001-1005
栏目:
基础研究
出版日期:
2022-11-05

文章信息/Info

Title:
Effect of circadian clock gene Bmal1 on the proliferation of colon cancer cell
作者:
张博汝魏柏石晓雅谢梦丽
(华中科技大学同济医学院附属梨园医院肿瘤科,湖北 武汉 430077)
Author(s):
ZHANG BoruWEI BaiSHI XiaoyaXIE Mengli
(Department of Oncology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,Hubei Province,China)
关键词:
Bmal1基因结肠癌细胞缺氧诱导因子-1α血管内皮生长因子
Keywords:
Bmal1 genecolon cancer cellhypoxia-inducible factor-1αvascular endothelial growth factor
分类号:
R574.62
DOI:
10.7683/xxyxyxb.2022.11.001
文献标志码:
A
摘要:
目的 探讨生物钟基因Bmal1基于缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对结肠癌细胞增殖的影响。方法 将对数生长期结肠癌MC38细胞随机分为对照组和Bmal1基因沉默组,2组细胞按照HiPerFect 转染试剂说明书分别转染阴性对照干扰小RNA(siRNA)和Bmal1 siRNA。细胞转染后0、24、48 h,采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)法检测2组细胞增殖能力;细胞转染后48 h,采用实时荧光定量聚合酶链式反应法检测2组细胞中Bmal1、HIF-1α、VEGF mRNA的相对表达量,Western blot法检测2组细胞Bmal1、HIF-1α、VEGF蛋白的相对表达量。结果 转染后0 h, 2组细胞增殖能力比较差异无统计学意义(P>0.05);转染后24、48 h,Bmal1基因沉默组细胞增殖能力显著低于对照组(P<0.05)。细胞转染后48 h,Bmal1基因沉默组细胞中Bmal1 mRNA和蛋白相对表达量显著低于对照组(P<0.05),Bmal1基因沉默组细胞中HIF-1α和VEGF的mRNA和蛋白相对表达量显著低于对照组(P<0.05)。 结论 沉默Bmal1基因可抑制结肠癌细胞的增殖,其机制可能与抑制HIF-1α/VEGF信号通路有关。
Abstract:
Objective To investigate the effect of circadian clock gene Bmal1 on the proliferation of colon cancer cell based on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway.Methods MC38 cells of colon cancer in logarithmic growth stage were randomly divided into control group and Bmal1 gene silencing group.The cells in the two groups were transfected with negative control small interfering RNA (siRNA) and Bmal1 siRNA according to the instructions of HiPerFect transfection reagent,respectively.At 0,24,48 hours after transfection,the proliferation ability of cells in the two groups was detected by the cell counting kit-8 (CCK-8) assay.At 48 hours after transfection,the relative expressions of Bmal1,HIF-1α and VEGF mRNA in cells in the two groups were detected by real-time fluorescence quantitative polymerase chain reaction,the relative expressions of Bmal1,HIF-1α and VEGF protein in the cells in the two groups were detected by Western Blot.Results There was no significant difference in the cell proliferation ability between the two groups at 0 hour after transfection (P>0.05).At 24 and 48 hours after transfection,the proliferation activity of cells in the Bmal1 gene silencing group was significantly lower than that in the control group (P<0.05).At 48 hours after transfection,the relative expressions of Bmal1 mRNA and protein in cells in the Bmal1 gene silencing group were significantly lower than those in the control group (P<0.05),and the relative expressions of HIF-1α and VEGF mRNA and protein in cells in the Bmal1 gene silencing group were significantly lower than those in the control group (P<0.05).Conclusion Bmal1 gene silencing can inhibit the proliferation of colon cancer cells,and the mechanism may be related to the inhibition of HIF-1α/VEGF signaling pathway.

参考文献/References:

[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[2] PAPANTONIOU K,CASTAO-VINYALS G,ESPINOSA A,et al.Shift work and colorectal cancer risk in the MCC-Spain case-control study[J].Scand J Work Environ Health,2017,43(3):250-259.
[3] BASS J,TAKAHASHI J S.Circadian integration of metabolism and energetics[J].Science,2010,330(6009):1349-1354.
[4] TROTT A J,MENET J S.Regulation of circadian clock transcriptional output by CLOCK:BMAL1[J].PLoS Genet,2018,14(1):e1007156.
[5] STOKES K,COOKE A,CHANG H,et al.The circadian clock gene BMAL1 Coordinates Intestinal Regeneration[J].Cell Mol Gastroenterol Hepatol,2017,4(1):95-114.
[6] MOMMA T,OKAYAMA H,SAITOU M,et al.Expression of circadian clock genes in human colorectal adenoma and carcinoma[J].Oncol Lett,2017,14(5):5319-5325.
[7] 程玉,郝美玲,薛晶,等.节律因子BMAL1通过SHH信号转导通路影响胃癌MGC-803 细胞的增殖[J].中国癌症杂志,2020,30(9):661-666.
CHENG Y,HAO M L,XUE J,et al.BMAL1 infuences proliferation of gastric cancer MGC-803 cells through SHH signaling pathway[J].China Oncol,2020,30(9):661-666.
[8] LUO W,WANG Y.Hypoxia mediates tumor malignancy and therapy resistance[J].Adv Exp Med Biol,2019,1136:1-18.
[9] KIERANS S J,TAYLOR C T.Regulation of glycolysis by the hypoxia-inducible factor (HIF):implications for cellular physiology[J].J Physiol,2021,599(1):23-37.
[10] LEE S,HALLIS S P,JUNG K A,et al.Impairment of HIF-lα-mediated metabolic adaption by NRF2-silencing in breast cancer cells[J].Redox Biol,2019,24:101210.
[11] TONG W W,TONG G H,LIU Y.Cancer stem cells and hypoxia-inducible factors(Review)[J].Int J Oncol,2018,53(2):469-476.
[12] ROMA-RODRIGUES C,MENDES R,BAPTISTA P V,et al.Targeting tumor microenvironment for cancer therapy[J].Int J Mol Sci,2019,20(4):840.
[13] KHAN K A,KERBEL R S.Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa[J].Nat Rev Clin Oncol,2018,15(5):310-324.
[14] MARTIN J D,SEANO G,JAIN R K.Normalizing function of tumor vessels:progress opportunities,and challenges[J].Annu Rev Physiol,2019,81:505-534.
[15] DEWANGAN J,KAUSHIK S,RATH S K,et al.Centchroman regulates breast cancer angiogenesis via inhibition of HIF-1α/VEGFR2 signalling axis[J].Life Sci,2018,193:9-19.
[16] MANELLA G,AVIRAM R,BOLSHETTE N,et al.Hypoxia induces a time-and tissue-specific response that elicits intertissue circadian clock misalignment[J].Proc Natl Acad Sci U S A,2020,117(1):779-786.
[17] WU Y,TANG D,LIU N,et al.Reciprocal regulation between the circadian clock and hypoxia signaling at the genome level in mammals[J].Cell Metab,2017,25(1):73-85.
[18] SUYAMA K,SILAGI E S,CHOI H,et al.Circadian factors BMAL1 and RORa control HIF-lα transcriptional activity in nucleus pulposus cells:implications in maintenance of intervertebral disc health[J].Oncotarget,2016,7(17):23056-23071.
[19] SOLECKI G,OSSWALD M,WEBER D,et al.Differential effects of ang-2/VEGF-A inhibiting antibodies in combination with radio or chemotherapyin glioma[J].Cancers(Basel),2019,11(3):314.
[20] 孙宪春,杨海燕,张翼飞,等.MTA1调控HIF-1α/VEGF通路作用于胰腺癌细胞增殖和迁移能力的研究[J].临床和实验医学杂志,2020,19(3):267-271.
SUN X C,YANG H Y,ZHANG Y F,et al.Effect of MTA1 on the proliferation and migration of pancreatic cancer cells by regulating HIF-1α/VEGF pathway[J].J Clin Exp Med,2020,19(3):267-271.
[21] WANG F,LI C,HAN F,et al.BMALl may be involved in angiogenesis and peritumoral cerebral edema of human glioma by regulating VEGF and ANG2[J].Aging(Albany NY),2021,13(22):24675-24685.

更新日期/Last Update: 2022-11-05