Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro
Because breast cancer is complicated at the pathological, histological, clinical, and molecular levels, identification of new genetic targets against carcinogenic pathways is required to generate clinically relevant treatment options. In the current study, ubiquitin-specific protease 7 (USP7), which regulates various cellular pathways including Mdm2, p53, and NF-kappa B, was selected as a potential gene editing strategy for breast cancer in vitro. Anticancer activity of USP7 gene suppression has been evaluated through cell proliferation, gene expression, cell cycle, sphere dissemination, and cell migration analysis. Here, siRNA and shRNA strategies and an allosteric small-molecule inhibitor of USP7 were used to define potential anticancer activity against MCF7 and T47D human breast cancer cell lines. Both blockage of deubiquitination by p5091 and knockdown of USP7 reduced cell proliferation, cell migration, colony formation, and sphere dissemination for both MCF7 and T47D breast cancer cell lines. Restriction of USP7 activity strongly enhanced apoptotic gene expression and reduced metastatic ability of breast cancer cell lines. This study describes one potential molecular target for the suppression of breast cancer proliferation and metastasis. Identification of USP7 as a promising gene editing candidate might open up the possibility of new molecular drug research in targeting the ubiquitination pathway in cancer.
___
- Al-Mahmood S, 2018, DRUG DELIV TRANSL RE, V8, P1483, DOI 10.1007/s13346-018-0551-3
- Amerik AY, 2004, BBA-MOL CELL RES, V1695, P189, DOI 10.1016/j.bbamcr.2004.10.003
- Borner C, 2014, CELL DEATH DIFFER, V21, P187, DOI 10.1038/cdd.2013.169
- Brahemi G, 2010, J MED CHEM, V53, P2757, DOI 10.1021/jm901757t
- Carra G, 2017, ONCOTARGET, V8, P35508, DOI 10.18632/oncotarget.16348
- Chen JD, 2016, CSH PERSPECT MED, V6, DOI 10.1101/cshperspect.a026104
- Ciechanover A, 2013, BIOORGAN MED CHEM, V21, P3400, DOI 10.1016/j.bmc.2013.01.056
- Demirci S, 2019, CHEM BIOL DRUG DES, V94, P1584, DOI 10.1111/cbdd.13575
- Dey A, 2007, CELL CYCLE, V6, P2178, DOI 10.4161/cc.6.17.4643
- DiGirolamo CM, 1999, BRIT J HAEMATOL, V107, P275, DOI 10.1046/j.1365-2141.1999.01715.x
- Dogan A, 2014, BIOL TRACE ELEM RES, V162, P72, DOI 10.1007/s12011-014-0104-7
- Gallo LH, 2017, CELL CYCLE, V16, P634, DOI 10.1080/15384101.2017.1288326
- Gasco M, 2002, BREAST CANCER RES, V4, P70, DOI 10.1186/bcr426
- Gupta A, 2019, BIOMED PHARMACOTHER, V109, P484, DOI 10.1016/j.biopha.2018.10.155
- Hoeller D, 2009, NATURE, V458, P438, DOI 10.1038/nature07960
- Hosseini H, 2016, NATURE, V540, P552, DOI 10.1038/nature20785
- Hu T, 2019, MOL CARCINOGEN, V58, P42, DOI 10.1002/mc.22905
- Huang KT, 2004, BIOTECHNIQUES, V37, P406, DOI 10.2144/04373ST05
- Kessler BM, 2007, J PROTEOME RES, V6, P4163, DOI 10.1021/pr0702161
- King RW, 1996, SCIENCE, V274, P1652, DOI 10.1126/science.274.5293.1652
- Kuo CT, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-04718-1
- Lai H, 2004, BREAST CANCER RES TR, V83, P57, DOI 10.1023/B:BREA.0000010699.53742.60
- Li SY, 2017, AM J CANCER RES, V7, P448 .
- Lim LY, 2009, BRIT J CANCER, V101, P1606, DOI 10.1038/sj.bjc.6605335
- Liu M, 2016, CELL MOL GASTROENTER, V2, P63, DOI 10.1016/j.jcmgh.2015.08.008
- Lyden D, 2011, CANC METASTASIS BIOL .
- Mali Shrikant, 2013, Indian J Hum Genet, V19, P3, DOI 10.4103/0971-6866.112870
- Morra F, 2017, ONCOTARGET, V8, P31815, DOI 10.18632/oncotarget.16463
- Mourtzoukou D, 2018, UBIQUITINATION GOVER, P179
- Nakanishi A, 2014, INT J ONCOL, V44, P1813, DOI 10.3892/ijo.2014.2377
- Navarro E, 2015, CLIN CHIM ACTA, V439, P231, DOI 10.1016/j.cca.2014.10.017
- Nijman SMB, 2005, CELL, V123, P773, DOI 10.1016/j.cell.2005.11.007
- Ohta T, 2004, ONCOGENE, V23, P2079, DOI 10.1038/sj.onc.1207371
- Oren M, 2003, CELL DEATH DIFFER, V10, P431, DOI 10.1038/sj.cdd.4401183
- Pal A, 2014, BREAST CANCER RES, V16, DOI 10.1186/s13058-014-0461-3
- Parrales A, 2015, FRONT ONCOL, V5, DOI 10.3389/fonc.2015.00288
- Siegel RL, 2020, CA-CANCER J CLIN, V70, P7, DOI 10.3322/caac.21590
- Simpson PT, 2005, J PATHOL, V205, P248, DOI 10.1002/path.1691
- Song MS, 2008, EMBO J, V27, P1863, DOI 10.1038/emboj.2008.115
- Sowa ME, 2009, CELL, V138, P389, DOI 10.1016/j.cell.2009.04.042
- Tavana O, 2018, CELL CYCLE, V17, P823, DOI 10.1080/15384101.2018.1456293
- Wang MY, 2017, CELL PHYSIOL BIOCHEM, V43, P1755, DOI 10.1159/000484062
- Wang Q, 2016, J CLIN INVEST, V126, P2205, DOI 10.1172/JCI85747
- Wang ZR, 2019, FRONT PHARMACOL, V10, DOI 10.3389/fphar.2019.00427
- WEISWALD LB, 2014, NEO, V17, P1, DOI DOI 10.1016/J.NEO.2014.12.004
- Wirapati P, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr2124
- Xia XH, 2019, CANCER LETT, V465, P118, DOI 10.1016/j.canlet.2019.09.003
- Yoshimura T, 2016, ONCOTARGET, V7, P49065, DOI 10.18632/oncotarget.7529
- Yu S, 2017, BIOCHEM BIOPH RES CO, V486, P752, DOI 10.1016/j.bbrc.2017.03.114