肝细胞核因子-1α基因突变协同腺瘤样结肠息肉病基因突变对家族性腺瘤性息肉病细胞增殖的影响

doi:10.3877/cma.j.issn.2095-2015.2022.04.008

中华消化病与影像杂志(电子版) ›› 2022, Vol. 12 ›› Issue (04) : 228 -231. doi: 10.3877/cma.j.issn.2095-2015.2022.04.008

基础研究

肝细胞核因子-1α基因突变协同腺瘤样结肠息肉病基因突变对家族性腺瘤性息肉病细胞增殖的影响

杨翠萍¹, 杨晓金², 全旭¹, 谢玲¹, 吴云林¹, 陈平¹^,^†(

)

^1. 201801　上海，上海交通大学医学院附属瑞金医院北部院区消化科
^2. 332000　江西九江，九江市第一人民医院感控科；710061　西安，西安交通大学公共卫生学院

收稿日期:2022-06-05 出版日期:2022-08-01
通信作者: 陈平
基金资助:
嘉定区卫健委科研项目(2018-KY-01)

Effects of hepatocyte nuclear factor-1α mutation and adenomatous polyposis coli mutation on familial adenomatous polyposis cell proliferation

Cuiping Yang¹, Xiaojin Yang², Xu Quan¹, Ling Xie¹, Yunlin Wu¹, Ping Chen¹^,^†()

^1. Department of Gastroenterology, North District of Ruijin Hosptial, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
^2. Department of Infection Control, Jiujiang First People's Hospital, Jiujiang 332000, China; School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China

Received:2022-06-05 Published:2022-08-01
Corresponding author: Ping Chen

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引用本文：

杨翠萍, 杨晓金, 全旭, 谢玲, 吴云林, 陈平. 肝细胞核因子-1α基因突变协同腺瘤样结肠息肉病基因突变对家族性腺瘤性息肉病细胞增殖的影响[J]. 中华消化病与影像杂志(电子版), 2022, 12(04): 228-231.

Cuiping Yang, Xiaojin Yang, Xu Quan, Ling Xie, Yunlin Wu, Ping Chen. Effects of hepatocyte nuclear factor-1α mutation and adenomatous polyposis coli mutation on familial adenomatous polyposis cell proliferation[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2022, 12(04): 228-231.

目的

探讨肝细胞核因子-1α（HNF-1α）基因突变协同腺瘤样结肠息肉病基因（APC）突变对家族性腺瘤性息肉病（FAP）细胞增殖的影响。

方法

利用RNA干扰技术，构建HNF-1α基因突变协同APC突变细胞模型，通过MTT法、克隆形成、划痕试验、细胞迁移、细胞侵袭及致瘤等实验观察HNF-1α基因突变协同APC突变对FAP细胞的增殖能力。

结果

与单突变组比较，HNF-1α基因突变协同APC突变组FAP细胞具有较强的细胞克隆形成、细胞迁移、细胞侵袭及致瘤性。

结论

HNF-1α基因协同APC突变促进了FAP细胞增殖。

关键词: 家族性腺瘤性息肉病, 腺瘤样结肠息肉病, 肝细胞核因子-1α, 基因突变, 细胞增殖

Objective

To explore the effects of hepatocyte nuclear factor-1α (HNF-1α) mutation and adenomatous polyposis coli (APC) mutation on cell proliferation in familial adenomatous polyposis (FAP).

Methods

The cell model of HNF-1α combined with APC mutation was constructed by RNA interference technique. MTT assay, cell clonal formation, wound healing test, cell migration, cell invasion and tumorigenesis were used to obseve the effects of HNF-1α mutation and APC mutation on the proliferation ability of FAP cells.

Results

Compared with the control group, HNF-1α combined with APC mutation group showed stronger cell clonal formation, cell migration, cell invasion and tumorigenicity.

Conclusion

HNF-1α combined with APC mutation promotes the proliferation of FAP cells.

Key words: Familial adenomatous polyposis, Adenomatous polyposis coli, Hepatocyte nuclear factor-1α, Gene mutation, Cell proliferation

表1 引物序列

基因	上游引物	下游引物
APC	5'-TGA GGA ATT TGT CTT GGC GAG-3'	5'-GCA CTT CCC ATA GCA ATC CAT T-3'
HNF-1α	5'-CAG CGT GGC CTT GTT CTG TC-3'	5'-GAA ATG CCT GTG TGA GTA GGT GAT G-3'
β-actin	5'-GAA CTT CGA GCA AGA GAT GG-3'	5'-AGC ACT GTG TTG GCG TAC AG-3'

表1 引物序列

基因	上游引物	下游引物
APC	5'-TGA GGA ATT TGT CTT GGC GAG-3'	5'-GCA CTT CCC ATA GCA ATC CAT T-3'
HNF-1α	5'-CAG CGT GGC CTT GTT CTG TC-3'	5'-GAA ATG CCT GTG TGA GTA GGT GAT G-3'
β-actin	5'-GAA CTT CGA GCA AGA GAT GG-3'	5'-AGC ACT GTG TTG GCG TAC AG-3'

表2 HNF-1α基因突变协同APC突变对FAP细胞生长速度的影响（D₄₉₀）

组别	0 h	12 h	24 h	36 h	48 h	72 h	96 h
单突变组	0	5.1	10.1	15.9	25.2	37.1	52.1
双突变组	0	5.7	15.5	20.7	48.8	68.5	85.1
F值	4.425
P值	0.003

表2 HNF-1α基因突变协同APC突变对FAP细胞生长速度的影响（D₄₉₀）

组别	0 h	12 h	24 h	36 h	48 h	72 h	96 h
单突变组	0	5.1	10.1	15.9	25.2	37.1	52.1
双突变组	0	5.7	15.5	20.7	48.8	68.5	85.1
F值	4.425
P值	0.003

表3 HNF-1α基因突变协同APC突变对FAP细胞划痕愈合率的影响（%）

组别	24 h	72 h
单突变组	10.4	45.2
双突变组	20.7	70.8
F值	22.480
P值	0.002

表3 HNF-1α基因突变协同APC突变对FAP细胞划痕愈合率的影响（%）

组别	24 h	72 h
单突变组	10.4	45.2
双突变组	20.7	70.8
F值	22.480
P值	0.002

1	Half E, Bercovich D, Rozen P. Familial adenomatous polyposis [J]. Orphanet J Rare Dis, 2009, 4: 22.
2	Dinarvand P, Davaro EP, Doan JV, et al. Familial Adenomatous Polyposis Syndrome: An Update and Review of Extraintestinal Manifestations [J]. Arch Pathol Lab Med, 2019, 143(11): 1382-1398.
3	Kerr SE, Thomas CB, Thibodeau SN, et al. APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests [J]. J Mol Diagn, 2013, 15(1): 31-43.
4	Dolan S. Familial Adenomatous Polyposis: Development, Presentation, and Treatment Strategies [J]. Clin J Oncol Nurs, 2019, 23(2): 135-138.
5	Kumar P, Nagarajan A, Uchil PD. Analysis of Cell Viability by the MTT Assay [J]. Cold Spring Harb Protoc, 2018(6).
6	Cappiello F, Casciaro B, Mangoni ML. A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration [J]. J Vis Exp, 2018(133): 56825.
7	Roerink SF, Sasaki N, Lee-Six H, et al. Intra-tumour diversification in colorectal cancer at the single-cell level [J]. Nature, 2018, 556(7702): 457-462.
8	葛赛，王晰程. 家族性腺瘤性息肉病的诊疗进展 [J/CD]. 肿瘤综合治疗电子杂志, 2022, 8(1): 107-112.
9	高翔，肖剑春，杨庭楷, 等. 家族性腺瘤性息肉病合并十二指肠腺瘤的诊疗分析 [J]. 中华医学杂志, 2020, 100(28): 2203-2206.
10	Soons E, Bisseling TM, van Kouwen MCA, et al. Endoscopic management of duodenal adenomatosis in familial adenomatous polyposis-A case-based review [J]. United European Gastroenterol J, 2021, 9(4): 461-468.
11	汪昭明，袁捷，赵子夜, 等. 家族性腺瘤性息肉病的结直肠外表现研究进展 [J]. 山东医药, 2022, 62(11): 87-91.
12	Contessini-Avesani E, Botti F, Negri C, et al. Familial adenomatous polyposis. Surgical treatment: when and how [J]. Tech Coloproctol, 2004, 8 Suppl 2: s309-s314.
13	DE Marchis ML, Tonelli F, Quaresmini D, et al. Desmoid Tumors in Familial Adenomatous Polyposis [J]. Anticancer Res, 2017, 37(7): 3357-3366.
14	Galiatsatos P, Foulkes WD. Familial adenomatous polyposis [J]. Am J Gastroenterol, 2006, 101(2): 385-398.
15	Nguyen BH, Nguyen STB, Nguyen HH, et al. The Mutation Spectrum and Two Novel Point Mutations in the APC Gene in Vietnamese Patients with Familial Adenomatous Polyposis [J]. Asian Pac J Cancer Prev, 2022, 23(5): 1517-1522.
16	Nallamilli BRR, Hegde M. Detecting APC Gene Mutations in Familial Adenomatous Polyposis (FAP) [J]. Curr Protoc Hum Genet, 2017, 92: 10.8.1-10.8.16.
17	Fan Z, Fan K, Deng S, et al. HNF-1α promotes pancreatic cancer growth and apoptosis resistance via its target gene PKLR [J]. Acta Biochim Biophys Sin (Shanghai), 2020, 52(3): 241-250.
18	Thapar M, Grapp O, Fisher C. Management of hepatic adenomatosis [J]. Curr Gastroenterol Rep, 2015, 17(3): 12.
19	陈佳萍，周静，蒋涛, 等. HNF1A和HNF1B基因遗传变异与乳腺癌遗传易感性的关联研究 [J]. 南京医科大学学报(自然科学版), 2022, 42(2): 239-244, 251.
20	Auer TA, Fehrenbach U, Grieser C, et al. Hepatocellular adenomas: is there additional value in using Gd-EOB-enhanced MRI for subtype differentiation? [J]. Eur Radiol, 2020, 30(6): 3497-3506.
21	Cucchiara F, Petrini I, Passaro A, et al. Gene network Analysis Defines a Subgroup of Small Cell Lung Cancer patients With Short Survival [J]. Clin Lung Cancer, 2022: S1525-7304(22)00108-5.

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