Sufu突变通过调控Gli1促进肺腺癌恶性进展

刘继宏; 罗虎; 衣杏林; 周向东

doi:10.16016/j.2097-0927.202402071

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Sufu突变通过调控Gli1促进肺腺癌恶性进展

基础医学 | 更新时间：2026-01-09

- Sufu突变通过调控Gli1促进肺腺癌恶性进展
- Sufu mutation promotes malignant progression of lung adenocarcinoma by regulating Gli1
- 陆军军医大学学报 2024年46卷第10期页码：1142-1149
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院呼吸与危重症医学科
- 作者简介：
  
  [周向东，E-mail：xiangdongzhou@126.com ZHOU Xiangdong, E-mail: xiangdongzhou@126.com
- 基金信息：
- DOI：10.16016/j.2097-0927.202402071
  中图分类号： R394.3;R730.23;R734.2
- 收稿：2024-02-25，
  
  修回：2024-03-02，
  
  纸质出版：2024-05-30
- 稿件说明：
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刘继宏, 罗虎, 衣杏林, 等. Sufu突变通过调控Gli1促进肺腺癌恶性进展[J]. 陆军军医大学学报, 2024,46(10):1142-1149.

Jihong LIU, Hu LUO, Xinglin YI, et al. Sufu mutation promotes malignant progression of lung adenocarcinoma by regulating Gli1[J]. Journal of Army Medical University, 2024, 46(10): 1142-1149.
刘继宏, 罗虎, 衣杏林, 等. Sufu突变通过调控Gli1促进肺腺癌恶性进展[J]. 陆军军医大学学报, 2024,46(10):1142-1149. DOI： 10.16016/j.2097-0927.202402071.

Jihong LIU, Hu LUO, Xinglin YI, et al. Sufu mutation promotes malignant progression of lung adenocarcinoma by regulating Gli1[J]. Journal of Army Medical University, 2024, 46(10): 1142-1149. DOI： 10.16016/j.2097-0927.202402071.

摘要

目的

观察Sufu在肺腺癌中的突变情况以及Sufu突变后对Gli1转录调控的变化，探讨Sufu对肺腺癌进展的作用。

方法

通过cBioPortal网站获取Sufu在肺癌中的突变情况；构建4个Sufu单碱基突变载体；在肺腺癌细胞株(A549和H1975)中分别对Sufu进行过表达和敲除；通过细胞划痕实验检测Sufu对肺腺癌细胞迁移能力的影响；通过RT-qPCR、细胞免疫荧光和双荧光素酶报告基因实验观测Sufu突变后对Gli1转录水平的影响。

结果

cBioPortal网站数据显示: Sufu在肺腺癌中突变率分别为11.76%(肺鳞癌: 2/17)、0.96%(肺腺癌: 6/625)、1.01%(小细胞肺癌: 4/396)和0.69%(非小细胞肺癌: 77/11 227)；Sufu发生突变后，肺癌患者中位生存期显著降低[54.34(未突变组)

38.00(突变组)个月，

=1.943，

0.05

]

；A549细胞对Sufu敲除敏感，能显著上调Gli1的转录水平(

0.05)；在A549和H1975中，过表达Sufu能抑制细胞迁移(

0.05)；Sufu突变后，Gli1细胞定位未发生明显改变；Sufu-T411M突变能上调Gli1的转录水平(

0.05)。

结论

Sufu对肺腺癌转移有抑制作用，Sufu具有成为肺腺癌转移治疗靶点的潜力。

Abstract

Objective

To explore the effect of Sufu on lung adenocarcinoma by observing its mutation and the changes in Gli1 transcription after its mutation.

Methods

cBioPortal for Cancer Genomics was used to obtain the mutation status of Sufu in lung cancer. Four Sufu single base mutation vectors were constructed and transfected into lung adenocarcinoma cell lines A549 and H1975 to establish cells with Sufu overexpression and knockout. Wounding healing assay was employed to determine the effect of Sufu on cell migration

and RT-qPCR

immunofluorescence assay and dual luciferase reporter gene assay were utilized to explore the changes in Gli1 transcription after Sufu mutation.

Results

cBioPortal data showed that the mutation rate of Sufu in lung cancer was 11.76% in squamous cell carcinoma (2/17)

0.96% in adenocarcinoma (6/625)

1.01% in small cell lung cancer (4/396)

and 0.69% in non-small cell lung cancer (77/11 227). The median survival of lung cancer patients was significantly decreased in those with Sufu mutation than those without (38.00

54.34 months

=1.943

0.05). A549 cells were sensitive to Sufu knockout

and it resulted in significant increase of the transcription level of Gli1 (

0.05). Overexpression of Sufu inhibited cell migration ability in both A549 and H1975 cells (

0.05). Sufu mutation had no significant influence on the location of Gli1 in the cells. The Sufu-T411M mutation up-regulated the the transcription level of Gli1 (

0.05).

Conclusion

Sufu has an inhibitory effect on lung adenocarcinoma metastasis

and can be regarded as a potential target for lung adenocarcinoma metastasis.

关键词

Keywords

references

ZHANG Y T, VACCARELLA S, MORGAN E, et al . Global variations in lung cancer incidence by histological subtype in 2020: a population-based study[J ] . Lancet Oncol, 2023, 24 (11): 1206-1218. DOI: 10.1016/S1470-2045(23)00444-8.

HANNA A, SHEVDE L A. Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment[J]. Mol Cancer, 2016, 15: 24. DOI: 10.1186/s12943-016-0509-3.

AMAKYE D, JAGANI Z, DORSCH M. Unraveling the therapeutic potential of the Hedgehog pathway in cancer[J]. Nat Med, 2013, 19(11): 1410-1422. DOI: 10.1038/nm.3389.

LO H W, ZHU H, CAO X Y, et al . A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion[J ] . Cancer Res, 2009, 69(17): 6790-6798. DOI: 10.1158/0008-5472.CAN-09-0886.

WANGY, HSU J M, KANG Y A, et al . Oncogenic functions of Gli1 in pancreatic adenocarcinoma are supported by its PRMT1-mediated methylation[J ] . Cancer Res, 2016, 76(23): 7049-7058. DOI: 10.1158/0008-5472.CAN-16-0715.

GUERRINI-ROUSSEAU L, DUFOUR C, VARLET P, et al . Germline SUFU mutation carriers and medulloblastoma: clinical characteristics, cancer risk, and prognosis[J ] . Neuro-oncology, 2018, 20(8): 1122-1132. DOI: 10.1093/neuonc/nox228.

YANG H, FU H L, WANG B, et al . Exosomal miR-423-5p targets SUFU to promote cancer growth andmetastasis and serves as a novel marker for gastric cancer[J ] . Mol Carcinog, 2018, 57(9): 1223-1236. DOI: 10.1002/mc.22838.

FANG K, DU S, SHEN D C, et al . SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway[J ] . iScience, 2022, 25(7): 104618. DOI: 10.1016/j.isci.2022.104618.

HERBST R S, MORGENSZTERN D, BOSHOFF C. The biology and management of non-small cell lungcancer[J]. Nature, 2018, 553(7689): 446-454. DOI: 10.1038/nature25183.

TOLOSA E J, FERNANDEZ-BARRENA M G, IGUCHI E, et al . GLI1/GLI2 functional interplay is required to control Hedgehog/GLI targets gene expression[J ] . Biochem J, 2020, 477(17): 3131-3145. DOI: 10.1042/BCJ20200335.

LEI X P, LI Z, ZHONG Y H, et al . Gli1 promotes epithelial-mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability[J ] . Acta Pharm Sin B, 2022, 12(10): 3877-3890. DOI: 10.1016/j.apsb.2022.05.024.

DENG Y R, PENG D Z, XIAO J, et al . Inhibition of the transcription factor ZNF281 by SUFU to suppress tumor cell migration[J ] . Cell Death Differ, 2023, 30(3): 702-715. DOI: 10.1038/s41418-022-01073-1.

GHANDI M, HUANG F W, JANÉ-VALBUENA J, et al . Next-generation characterization of the Cancer Cell Line Encyclopedia[J ] . Nature, 2019, 569(7757): 503-508. DOI: 10.1038/s41586-019-1186-3.

赖舒, 张玉方. 石榴皮多酚对大鼠应激性胃溃疡的保护作用及与Gli1-Gli2-Sufu信号通路和细胞因子水平改变的关系[J]. 第三军医大学学报, 2017, 39(19): 1913-1918. DOI: 10.16016/j.1000-5404.201704083.

LAI S, ZHANG Y F. Protective effects of pomegranate peel polyphenols against stress gastric ulcer in rats and their effect on cytokine levels and Gli1-Gli2-Sufu signaling pathway[J]. J Third Mil Med Univ, 2017, 39(19): 1913-1918. DOI: 10.16016/j.1000-5404.201704083.

PARADISE B D, GAINULLIN V G, ALMADA L L, et al . SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer[J ] . Biochem J, 2023, 480(15): 1199-1216. DOI: 10.1042/BCJ20220439.

SMITH M J, BEETZ C, WILLIAMS S G, et al . Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations[J ] . J Clin Oncol, 2014, 32(36): 4155-4161. DOI: 10.1200/JCO.2014.58.2569.

QUATANNENS D, VERHOEVEN Y, VAN DAM P, et al . Targeting hedgehog signaling in pancreatic ductal adenocarcinoma[J ] . Pharmacol Ther, 2022, 236: 108107. DOI: 10.1016/j.pharmthera.2022.108107.

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