雷帕霉素减缓转基因小鼠肝细胞癌进展

doi:10.16352/j.issn.1001-6325.2023.08.1241

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (8): 1241-1246.doi: 10.16352/j.issn.1001-6325.2023.08.1241

雷帕霉素减缓转基因小鼠肝细胞癌进展

林映雪¹, 崔海鹏^2*, 王爱国^3*, 姚银辉¹, 赵娟²

1.承德医学院附属医院药学部,河北承德 067000;
2.承德医学院病理生理学教研室,河北承德 067000;
3.大连医科大学实验动物中心,辽宁大连 116044

收稿日期:2023-02-06 修回日期:2023-05-30 出版日期:2023-08-05 发布日期:2023-07-26
通讯作者: ^*han984746810@163.com;wangaiguotl@hotmail.com
基金资助:
河北省自然科学基金(H2020406011);河北省医学科学研究课题计划(20200183);河北省高等学校科学研究青年基金(QN2023017)

Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice

LIN Yingxue¹, CUI Haipeng^2*, WANG Aiguo^3*, YAO Yinhui¹, ZHAO Juan²

1. Department of Pharmacy, Affiliated Hospital of Chengde Medical University, Chengde 067000;
2. Department of pathophysiology, Chengde Medical University, Chengde 067000;
3. Laboratory Animal Center, Dalian Medical University, Dalian 116044, China

Received:2023-02-06 Revised:2023-05-30 Online:2023-08-05 Published:2023-07-26
Contact: ^*han984746810@163.com;wangaiguotl@hotmail.com

摘要/Abstract

摘要： 目的探究雷帕霉素(rapamycin)对H-ras 12V转基因小鼠肝细胞癌(HCC)进展的影响。方法 miRNA高通量测序检测转基因小鼠肝癌及癌旁组织中miRNA表达水平,采用雷帕霉素对转基因小鼠进行治疗干预,形态学检测小鼠肿瘤的变化,RT-qPCR检测miR-183 mRNA表达水平,Western blot检测mTOR、ERK蛋白及miR-183靶基因PDCD4蛋白表达水平。结果肝癌组织中miR-183表达水平较癌旁组织显著升高(P＜0.01),PDCD4蛋白水平较癌旁组织显著降低(P＜0.05)。雷帕霉素干预后,与对照组相比,雷帕霉素组肝肿瘤整体总数显著下降(P＜0.05),肝系数显著降低(P＜0.05),ERK磷酸化水平显著升高(P＜0.05),miR-183表达水平显著下降(P＜0.05),其靶基因PDCD4表达水平显著升高(P＜0.05)。结论雷帕霉素可减缓H-ras 12V转基因小鼠肝癌的进展。

关键词: 肝细胞癌, 雷帕霉素, miR-183, 程序性细胞死亡因子4

Abstract: Objective Exploring the influence of rapamycin on the progressing of hepatocellular carcinoma(HCC) in H-ras 12V transgenic mice. Methods The expression level of miRNA in liver tissue and peritumor tissue of transgenic mice was detected by high-throughput sequencing of miRNAs. Treatment of transgenic mice with rapamycin and the changes of tumor morphology were detected. The miR-183 expression levels were detected by RT-qPCR. The protein expression levels of mTOR, ERK and PDCD4, the downstream target gene of miR-183, were detected by Western blot. Results Compared with the peritumor tissue, the miR-183 expression in hepatocellular carcinoma tissue was increased significantly (P＜0.01). The protein expression levels of PDCD4 were decreased significantly(P＜0.05). Compared with the control group, after intervention with rapamycin, the counting of liver tumors decreased significantly(P＜0.05). The liver co-efficient decreased significantly(P＜0.05). The ERK phosphorylation increased significantly (P＜0.05). The miR-183 expression was decreased significantly (P＜0.05). The protein level of PDCD4 increased significantly (P＜0.05). Conclusions Rapamycin can alleviate hepatocellular carcinoma progression in H-ras 12V transgenic mice.

Key words: hepatocellular carcinoma, rapamycin, miR-183, PDCD4

中图分类号:

R735.7

林映雪, 崔海鹏, 王爱国, 姚银辉, 赵娟. 雷帕霉素减缓转基因小鼠肝细胞癌进展[J]. 基础医学与临床, 2023, 43(8): 1241-1246.

LIN Yingxue, CUI Haipeng, WANG Aiguo, YAO Yinhui, ZHAO Juan. Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice[J]. Basic & Clinical Medicine, 2023, 43(8): 1241-1246.

参考文献 15

[1]	Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification[J]. Adv Cancer Res, 2021,149:1-61.
[2]	Zhang J, Li H, Dong J, et al. Omics-based identification of shared and gender disparity routes in Hras12V-induced hepatocarcinogenesis: an important role for Dlk1-Dio3 genomic imprinting region[J]. Front Genet, 2021, 12: 620594. doi: 10.3389/fgene.2021.620594.
[3]	Wang AG, Moon HB, Lee MR, et al. Gender-dependent hepatic alterations in H-ras 12V transgenic mice[J]. Hepatol, 2005, 43: 836-844.
[4]	Mukherjee S, Mukherjee U. A comprehensive review of immunosuppression used for liver transplantation[J]. J Transplant, 2009: 701464. doi: 10.1155/2009/701464.
[5]	Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice[J]. Nature, 2009, 460: 392-395.
[6]	Malagelada C, Jin ZH, Jackson-Lewis V, et al. Rapamy-cin protects against neuron death in in vitro and in vivo models of Parkinson's disease[J]. J Neurosci, 2010, 30: 1166-1175.
[7]	Hua H, Kong Q, Zhang H, et al. Targeting mTOR for cancer therapy[J]. J Hematol Oncol, 2019, 12:71. doi: 10.1186/s13045-019-0754-1.
[8]	Sun L, Yan Y, Lv H, et al. Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth[J]. Cell Chem Biol, 2022, 29: 373-385.
[9]	Chappell WH, Steelman LS, Long JM, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health[J]. Oncotarget, 2011, 2:135-164.
[10]	Albert L, Karsy M, Murali R, et al. Inhibition of mTOR activates the MAPK pathway in glioblastoma[J]. Cancer Genom Proteom, 2009, 6: 255-261.
[11]	马家玲, 高艳平. miR-183靶向Bnip3l对缺氧/复氧的小鼠海马神经元细胞线粒体自噬的影响[J]. 基础医学与临床, 2021, 41: 698-703.
[12]	Zhu W, Liu X, He J, et al. Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study[J]. BMC Cancer, 2011, 11: 393. doi:10.1186/1471-2407-11-393.
[13]	Stephan C, Jung M, Rabenhorst S, et al. Urinary miR-183 and miR-205 do not surpass PCA3 in urine as predictive markers for prostate biopsy outcome despite their highly dysregulated expression in prostate cancer tissue[J]. Clin Chem Lab Med, 2015, 53: 1109-1118.
[14]	Li J, Fu H, Xu C, et al. MiR-183 inhibits TGF-β1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells[J]. BMC Cancer, 2010, 10: 354-363.
[15]	Niu Y, Liu F, Wang X, et al. miR-183-5p promotes HCC migration/invasion via increasing aerobic glycolysis [J]. Onco Targets Ther, 2021, 14: 3649-3658.

雷帕霉素减缓转基因小鼠肝细胞癌进展

Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 15

编辑推荐

Metrics

本文评价

[1]	依马木买买提江·阿布拉, 帕哈尔丁·白克热, 易超, 佟庆. 血浆hsa_circ_005230在原发性肝细胞癌诊断和预后评估中的临床价值[J]. 基础医学与临床, 2023, 43(9): 1417-1422.
[2]	邹瑾, 何向蕾, 张欣, 陈日萍, 张宇, 胡帅悦, 应士波. 蛋白质精氨酸残基化学修饰酶PADs与PRMTs在人肝癌细胞系中的表达[J]. 基础医学与临床, 2023, 43(6): 898-903.
[3]	冀梦蝶, 苑赞, 卞晓翠, 杨玉容, 郭鑫, 王琦, 陈阳. 人肝癌细胞系HepG2和Huh7中的基因组拷贝数变异分析[J]. 基础医学与临床, 2023, 43(6): 960-966.
[4]	刘婷婷, 韩超, 赵小玲, 孔为民. 二甲双胍抑制人宫颈鳞癌细胞系SiHa和CaSKi增殖及促进细胞凋亡[J]. 基础医学与临床, 2023, 43(2): 283-288.
[5]	刘爱霞, 张浩, 孙杰, 杨丽华, 赵晓涛. GPS2对肝癌细胞系MHCC-97H增殖、迁移与侵袭的调控作用[J]. 基础医学与临床, 2023, 43(12): 1784-1791.
[6]	查娜, 郝丹丹, 李天柱. microRNAs通过Hippo通路抑制肝细胞癌发生的研究进展[J]. 基础医学与临床, 2023, 43(12): 1871-1875.
[7]	贾楠, 王志莲. CALCOCO1与恶性肿瘤的发生发展[J]. 基础医学与临床, 2023, 43(11): 1733-1737.
[8]	黄驿胜, 叶启文, 王竞枫. miR-203a-3p抑制人肝癌细胞系增殖[J]. 基础医学与临床, 2023, 43(1): 87-94.
[9]	王平, 徐作军, 徐凯峰. 肺多发结节囊性病变罕见原因结节性硬化症1例[J]. 基础医学与临床, 2022, 42(9): 1424-1427.
[10]	张新格, 马洁, 王庆志, 辛悦, 杨晨妍, 熊熙文. 肠上皮Depdc5/mTORC1信号轴调控小鼠小肠上皮稳态[J]. 基础医学与临床, 2022, 42(8): 1213-1219.
[11]	赵钰珊, 冀梦蝶, 董昱诚, 郭鑫, 宋博渊, 陈阳. 肝细胞癌中EZH2基因相关的表观遗传调控机制[J]. 基础医学与临床, 2022, 42(6): 864-870.
[12]	王玉敏, 陈济超, 王洪权, 王金华, 唐博. MicroRNAs靶向脂代谢重编程参与肝细胞癌发生的研究进展[J]. 基础医学与临床, 2022, 42(12): 1930-1934.
[13]	黄婷, 李真真, 白杨, 刘惠双. 益生菌改善高脂高糖饲养诱导的肥胖小鼠脂代谢紊乱[J]. 基础医学与临床, 2021, 41(9): 1260-1265.
[14]	李凯, 王亚南. 氢氧化钠增强雷帕霉素抑制Tsc2缺失的小鼠胚胎成纤维细胞的增殖[J]. 基础医学与临床, 2021, 41(7): 951-956.
[15]	吴娜, 王东, 白咸勇. 细胞自噬与肝细胞癌的研究进展[J]. 基础医学与临床, 2021, 41(10): 1514-1517.