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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

将 AHSA1 鉴定为乳腺癌的潜在治疗靶点：生物信息学分析和体外研究

卷 22, 期 2, 2022

发表于: 14 February, 2022

页: [142 - 152] 页: 11

弟呕挨: 10.2174/1568009622666220114151058

价格: $65

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摘要

背景：参苓白术散（SBP）是一种著名的中药（TCM）剂型，已广泛用于包括乳腺癌在内的癌症的辅助治疗。本研究旨在基于 SBP 的网络药理学确定乳腺癌治疗的潜在新靶点。 方法：通过分析药材与靶蛋白的关系，通过网络药理学分析确定多种药材在SBP中的潜在靶点。此外，通过比较乳腺癌组织与正常组织的数据，发现了两种乳腺癌表达谱中的上调基因。此后，通过生物信息学分析进一步分析了热休克蛋白90（HSP90）ATP酶活性1（AHSA1）激活剂在乳腺癌中的表达水平和预后，并构建了AHSA1结合蛋白的网络模块。此外，通过MTT、克隆形成试验和transwell试验验证了敲低AHSA1对乳腺癌细胞增殖、迁移和侵袭的影响。 结果：血管内皮生长因子 A (VEGFA)、细胞间粘附分子 1 (ICAM1)、趋化因子 (C-X-C 基序) 配体 8 (CXCL8)、AHSA1 和丝氨酸蛋白酶抑制剂家族 E 成员 1 (SERPINE1) 与 SBP 中的多种草药相关。 AHSA1 在乳腺癌组织中显着上调，并且与较差的总生存期和无疾病转移生存期呈正相关。此外，AHSA1的敲低显着抑制MCF-7和MDA-MB-231乳腺癌细胞的迁移和侵袭，但对增殖没有明显影响。此外，在与 AHSAl 结合的蛋白质中，由蛋白酶体、伴侣蛋白和热休克蛋白组成的网络紧密相连，这些蛋白质与多种癌症的预后不良有关。 结论：AHSA1与乳腺癌进展呈正相关，可能作为乳腺癌的新治疗靶点。

关键词: AHSA1，迁移，入侵，网络药理学，乳腺癌，申灵贝珠散。

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[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Daily, K.; Douglas, E.; Romitti, P.A.; Thomas, A. Epidemiology of de novo metastatic breast cancer. Clin. Breast Cancer, 2021, 21(4), 302-308.
[http://dx.doi.org/10.1016/j.clbc.2021.01.017] [PMID: 33750642]
[3]
Waks, A.G.; Winer, E.P. Breast cancer treatment: A review. JAMA, 2019, 321(3), 288-300.
[http://dx.doi.org/10.1001/jama.2018.19323] [PMID: 30667505]
[4]
Li, X.L.; Guo, X.Q.; Wang, H.R.; Chen, T.; Mei, N. Aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents. World J. Tradit. Chin. Med., 2020, 6(1), 12-25.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_33_19] [PMID: 32258091]
[5]
Xu, D.D.; Hou, X.Y.; Wang, O.; Wang, D.; Li, D.T.; Qin, S.Y.; Lv, B.; Dai, X.M.; Zhang, Z.J.; Wan, J.B.; Xu, F.G. A four-component combination derived from Huang-Qin decoction significantly enhances anticancer activity of irinotecan. Chin. J. Nat. Med., 2021, 19(5), 364-375.
[http://dx.doi.org/10.1016/S1875-5364(21)60034-1] [PMID: 33941341]
[6]
Li, Z.; Feiyue, Z.; Gaofeng, L. Traditional chinese medicine and lung cancer-from theory to practice. Biomed. Pharmacother., 2021, 137, 111381.
[http://dx.doi.org/10.1016/j.biopha.2021.111381] [PMID: 33601147]
[7]
Zhang, Y.; Lou, Y.; Wang, J.; Yu, C.; Shen, W. Research status and molecular mechanism of the traditional Chinese medicine and antitumor therapy combined strategy based on tumor microenvironment. Front. Immunol., 2021, 11, 609705.
[http://dx.doi.org/10.3389/fimmu.2020.609705] [PMID: 33552068]
[8]
Wan, L.Q.; Tan, Y.; Jiang, M.; Hua, Q. The prognostic impact of traditional Chinese medicine monomers on tumor-associated macrophages in non-small cell lung cancer. Chin. J. Nat. Med., 2019, 17(10), 729-737.
[http://dx.doi.org/10.1016/S1875-5364(19)30089-5] [PMID: 31703753]
[9]
Wang, Y.; Zhang, S.; Zhou, Q.; Meng, M.; Chen, W. Efficacy of shenlingbaizhu formula on irritable bowel syndrome: A systematic review. J. Tradit. Chin. Med., 2020, 40(6), 897-907.
[PMID: 33258340]
[10]
Yang, L.; Song, Y.; Jin, P.; Liu, Y.; Wang, Y.; Qiao, H.; Huang, Y. Shen-Ling-Bai-Zhu-San for ulcerative colitis: Protocol for a systematic review and meta-analysis. Medicine (Baltimore), 2018, 97(38), e12337.
[http://dx.doi.org/10.1097/MD.0000000000012337] [PMID: 30235688]
[11]
Fan, X.; Yang, Z.; Shi, Y. Shenling Baizhu San combined with chemotherapy, symptomatic treatment of cancer randomized controlled study. J Pract Tradit Chin Int., 2013, 27, 25-27.
[12]
Lin, X.; Xu, W.; Shao, M.; Fan, Q.; Wen, G.; Li, C.; Jing, L.; Sun, X. Shenling Baizhu San supresses colitis associated colorectal cancer through inhibition of epithelial-mesenchymal transition and myeloid-derived suppressor infiltration. BMC Complement. Altern. Med., 2015, 15, 126.
[http://dx.doi.org/10.1186/s12906-015-0649-9] [PMID: 25897964]
[13]
Zhao, J.; Lv, C.; Wu, Q.; Zeng, H.; Guo, X.; Yang, J.; Tian, S.; Zhang, W. Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke. Pharmacol. Res., 2019, 147, 104365.
[http://dx.doi.org/10.1016/j.phrs.2019.104365] [PMID: 31348992]
[14]
Hopkins, A.L. Network pharmacology. Nat. Biotechnol., 2007, 25(10), 1110-1111.
[http://dx.doi.org/10.1038/nbt1007-1110] [PMID: 17921993]
[15]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[16]
Yang, B.; Wang, N.; Wang, S.; Li, X.; Zheng, Y.; Li, M.; Song, J.; Zhang, F.; Mei, W.; Lin, Y.; Wang, Z. Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis. Biomed. Pharmacother., 2019, 112, 108607.
[http://dx.doi.org/10.1016/j.biopha.2019.108607] [PMID: 30784915]
[17]
Chen, J.J.; Shang, X.Y.; Han, F.Y.; Zhang, Y.; Zhao, D.; Yao, G.D.; Song, S.J. Network pharmacology predicted HDAC6 as a potential target of flavones from Daphne giraldii on hepatocellular carcinoma. Nat. Prod. Res., 2021, 35(18), 3171-3175.
[http://dx.doi.org/10.1080/14786419.2019.1693563] [PMID: 31741408]
[18]
Wandinger, S.K.; Richter, K.; Buchner, J. The Hsp90 chaperone machinery. J. Biol. Chem., 2008, 283(27), 18473-18477.
[http://dx.doi.org/10.1074/jbc.R800007200] [PMID: 18442971]
[19]
Maloney, A.; Workman, P. HSP90 as a new therapeutic target for cancer therapy: The story unfolds. Expert Opin. Biol. Ther., 2002, 2(1), 3-24.
[http://dx.doi.org/10.1517/14712598.2.1.3] [PMID: 11772336]
[20]
Panaretou, B.; Siligardi, G.; Meyer, P.; Maloney, A.; Sullivan, J.K.; Singh, S.; Millson, S.H.; Clarke, P.A.; Naaby-Hansen, S.; Stein, R.; Cramer, R.; Mollapour, M.; Workman, P.; Piper, P.W.; Pearl, L.H.; Prodromou, C. Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol. Cell, 2002, 10(6), 1307-1318.
[http://dx.doi.org/10.1016/S1097-2765(02)00785-2] [PMID: 12504007]
[21]
Tripathi, V.; Darnauer, S.; Hartwig, N.R.; Obermann, W.M. Aha1 can act as an autonomous chaperone to prevent aggregation of stressed proteins. J. Biol. Chem., 2014, 289(52), 36220-36228.
[http://dx.doi.org/10.1074/jbc.M114.590141] [PMID: 25378400]
[22]
Xu, W.; Beebe, K.; Chavez, J.D.; Boysen, M.; Lu, Y.; Zuehlke, A.D.; Keramisanou, D.; Trepel, J.B.; Prodromou, C.; Mayer, M.P.; Bruce, J.E.; Gelis, I.; Neckers, L. Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1. Nat. Commun., 2019, 10(1), 2574.
[http://dx.doi.org/10.1038/s41467-019-10463-y] [PMID: 31189925]
[23]
Shao, J.; Wang, L.; Zhong, C.; Qi, R.; Li, Y. AHSA1 regulates proliferation, apoptosis, migration, and invasion of osteosarcoma. Biomed. Pharmacother., 2016, 77, 45-51.
[http://dx.doi.org/10.1016/j.biopha.2015.11.008] [PMID: 26796264]
[24]
Zheng, D.; Liu, W.; Xie, W.; Huang, G.; Jiang, Q.; Yang, Y.; Huang, J.; Xing, Z.; Yuan, M.; Wei, M.; Li, Y.; Yin, J.; Shen, J.; Shi, Z. AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma. Signal Transduct. Target. Ther., 2021, 6(1), 25.
[http://dx.doi.org/10.1038/s41392-020-00387-1] [PMID: 33468990]
[25]
Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med., 2019, 8(5), 1958-1975.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[26]
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional Chinese medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123.
[http://dx.doi.org/10.3389/fphar.2019.00123] [PMID: 30846939]
[27]
Li, S. Network pharmacology evaluation method guidance-draft. World J. Tradit. Chin. Med., 2021, 7(1), 146.
[http://dx.doi.org/10.4103/wjtcm.wjtcm_11_21]
[28]
Zhang, Q.; Lu, S.; Li, T.; Yu, L.; Zhang, Y.; Zeng, H.; Qian, X.; Bi, J.; Lin, Y. ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway. J. Exp. Clin. Cancer Res., 2019, 38(1), 173.
[http://dx.doi.org/10.1186/s13046-019-1156-5] [PMID: 31023337]
[29]
Rosette, C.; Roth, R.B.; Oeth, P.; Braun, A.; Kammerer, S.; Ekblom, J.; Denissenko, M.F. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis, 2005, 26(5), 943-950.
[http://dx.doi.org/10.1093/carcin/bgi070] [PMID: 15774488]
[30]
Guo, P.; Huang, J.; Wang, L.; Jia, D.; Yang, J.; Dillon, D.A.; Zurakowski, D.; Mao, H.; Moses, M.A.; Auguste, D.T. ICAM-1 as a molecular target for triple negative breast cancer. Proc. Natl. Acad. Sci. USA, 2014, 111(41), 14710-14715.
[http://dx.doi.org/10.1073/pnas.1408556111] [PMID: 25267626]
[31]
Liu, Q.; Li, A.; Tian, Y.; Wu, J.D.; Liu, Y.; Li, T.; Chen, Y.; Han, X.; Wu, K. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev., 2016, 31, 61-71.
[http://dx.doi.org/10.1016/j.cytogfr.2016.08.002] [PMID: 27578214]
[32]
Singh, J.K.; Farnie, G.; Bundred, N.J.; Simões, B.M.; Shergill, A.; Landberg, G.; Howell, S.J.; Clarke, R.B. Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms. Clin. Cancer Res., 2013, 19(3), 643-656.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1063] [PMID: 23149820]
[33]
Azimi, I.; Petersen, R.M.; Thompson, E.W.; Roberts-Thomson, S.J.; Monteith, G.R. Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells. Sci. Rep., 2017, 7(1), 15140.
[http://dx.doi.org/10.1038/s41598-017-15474-7] [PMID: 29123322]
[34]
Freeberg, M.A.T.; Farhat, Y.M.; Easa, A.; Kallenbach, J.G.; Malcolm, D.W.; Buckley, M.R.; Benoit, D.S.W.; Awad, H.A. Serpine1 knockdown enhances MMP activity after flexor tendon injury in mice: Implications for adhesions therapy. Sci. Rep., 2018, 8(1), 5810.
[http://dx.doi.org/10.1038/s41598-018-24144-1] [PMID: 29643421]
[35]
Loibl, S.; Gianni, L. HER2-positive breast cancer. Lancet, 2017, 389(10087), 2415-2429.
[http://dx.doi.org/10.1016/S0140-6736(16)32417-5] [PMID: 27939064]
[36]
Baker-Williams, A.J.; Hashmi, F.; Budzyński, M.A.; Woodford, M.R.; Gleicher, S.; Himanen, S.V.; Makedon, A.M.; Friedman, D.; Cortes, S.; Namek, S.; Stetler-Stevenson, W.G.; Bratslavsky, G.; Bah, A.; Mollapour, M.; Sistonen, L.; Bourboulia, D. Co-chaperones TIMP2 and AHA1 competitively regulate extracellular HSP90:Client MMP2 activity and matrix proteolysis. Cell Rep., 2019, 28(7), 1894-1906.e6.
[http://dx.doi.org/10.1016/j.celrep.2019.07.045] [PMID: 31412254]

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