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骨转移肝细胞瘤差异高表达基因HDGF的筛选及细胞生物学效应的初步研究
Screening of hepatoma-derived growth factor with highly expression in HCC bone metastasis and its cellular biological effects
- 陆军军医大学学报 2024年46卷第23期 页码：2620-2628
- 作者机构：
1.402177 重庆，重庆医科大学附属永川医院骨科
2.400000 重庆，重庆大学附属肿瘤医院肝胆胰肿瘤中心
- 作者简介：
[ 邵高海, E-mail: shanggaohai567@163.comSHAO Gaohai, E-mail: shanggaohai567@163.com
- 基金信息：重庆市技术创新与应用发展专项重点项目(CSTB2022TIAD-KPX0172);重庆市技术创新与应用发展专项面上项目(2022yc-cxfz30008);重庆市自然科学基金面上(CSTB2023NSCQ-MSX0821);重庆市医药生物技术协会(cmba2022kyym-zkxmQ0012);沙坪坝区科卫联合医学科研项目(2023SQKWLH23)
DOI：10.16016/j.2097-0927.202404047
中图分类号： R730.23;R735.7;R738.1收稿：2024-04-13，
修回：2024-08-10，
纸质出版：2024-12-15
- 稿件说明：
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张希, 何永鹏, 邵高海. 骨转移肝细胞瘤差异高表达基因HDGF的筛选及细胞生物学效应的初步研究[J]. 陆军军医大学学报, 2024,46(23):2620-2628.
Xi ZHANG, Yongpeng HE, Gaohai SHAO. Screening of hepatoma-derived growth factor with highly expression in HCC bone metastasis and its cellular biological effects[J]. Journal of Army Medical University, 2024, 46(23): 2620-2628.
张希, 何永鹏, 邵高海. 骨转移肝细胞瘤差异高表达基因HDGF的筛选及细胞生物学效应的初步研究[J]. 陆军军医大学学报, 2024,46(23):2620-2628. DOI： 10.16016/j.2097-0927.202404047.
Xi ZHANG, Yongpeng HE, Gaohai SHAO. Screening of hepatoma-derived growth factor with highly expression in HCC bone metastasis and its cellular biological effects[J]. Journal of Army Medical University, 2024, 46(23): 2620-2628. DOI： 10.16016/j.2097-0927.202404047.
摘要
目的
2
探究肝癌衍生生长因子(hepatoma-derived growth factor
HDGF)在肝细胞癌(hepatocellular carcinoma
HCC)中的表达，以及其对DNA损伤、增殖、迁移、上皮-间质转化(epithelial mesenchymal transition
EMT)以及骨保护素(osteoprotegerin
OPG)的表达影响作用。
方法
2
分析GEO数据库中HCC骨转移患者与HCC非转移患者的肝脏肿瘤中mRNA的差异表达特征，筛选出差异最显著基因HDGF。利用qRT-PCR技术验证HDGF mRNA在转移能力不同的HCC细胞中的表达情况。分别通过γ-H2AX免疫荧光实验，分析不同组肝癌细胞的DNA损伤程度。采取Cell counting Kit-8试剂盒、集落形成实验和Transwell迁移实验检测HDGF对细胞增殖、迁移能力的影响。通过蛋白质印迹法，检测EMT相关蛋白Vimentin、E-cadherin在不同程度骨转移组HCC细胞中的表达差异。运用qRT-PCR技术和蛋白质印记法(western blot，WB)检测各组肝癌细胞中OPG的差异表达。
结果
2
HDGF在骨转移的HCC组织和高转移性HCC细胞系中高表达；HDGF高表达能够抑制细胞DNA损伤修复；HDGF能够促进HCC细胞系增殖、迁移；HDGF上调Vimentin的蛋白表达水平，同时下调E-cadherin的蛋白表达水平(
P
均＜0.05)，且HDGF过表达下调了OPG的表达。
结论
2
HDGF在骨转移肝细胞瘤中高表达，并可能通过促进EMT、迁移和增殖而促进骨转移。
Abstract
Objective
2
To investigate the expression of hepatoma-derived growth factor (HDGF) in hepatocellular carcinoma (HCC) and its effects on DNA damage
proliferation
migration
epithelial mesenchymal transition (EMT)
and expression of osteoprotegerin (OPG) in HCC cells.
Methods
2
GEO database was analyzed to obtain the expression features of differential expressed mRNAs in liver tumors between HCC patients with bone metastasis and those without
and then HDGF was found as the most significantly differentially expressed gene. The mRNA expression of HDGF was verified in the HCC cells with varying metastatic capabilities by qRT-PCR. DNA damage levels in different groups of liver cancer cells were analyzed through γ-H2AX immunofluorescence assay. The effects of HDGF on cell proliferation and migration were detected with CCK-8 assay
colony formation assay
and Transwell migration assay. Western blotting was employed to measure the expression of EMT-related proteins Vimentin and E-cadherin in HCC cells with various capacities of bone metastasis. Then qRT-PCR and Western blotting were performed to determine the differential expression of OPG in various groups of liver cancer cells.
Results
2
HDGF was highly expressed in HCC tissues with bone metastasis and in high-metastatic HCC cell lines. High expression of HDGF inhibited DNA damage repair. HDGF promoted the proliferation and migration of HCC cell lines. HDGF up-regulated the protein expression level of Vimentin while down-regulated that of E-cadherin (both
P
<
0.05)
and overexpression of HDGF down-regulated the expression of OPG.
Conclusion
2
HDGF is highly expressed in bone metastatic hepatocellular tumors and may promote bone metastasis by facilitating EMT
migration
and proliferation.
关键词
Keywords
references
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