Identification of genes associated with SiHa cell sensitivity to paclitaxel by CRISPR-Cas9 knockout screening

被引:0
作者
Wei, Wei [1 ]
He, Yue [1 ]
Wu, Yu-Mei [1 ]
机构
[1] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Dept Gynecol Oncol, 17 Qihelou St, Beijing 100006, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2018年 / 11卷 / 04期
关键词
Paclitaxel sensitivity; cervical cancer; CRISPR-Cas9; technology; TAXOL-INDUCED APOPTOSIS; BREAST-CANCER; PI3K/AKT/MTOR PATHWAY; MULTIDRUG-RESISTANCE; PROTEIN PHOSPHATASE; SIGNALING PATHWAYS; CARCINOMA CELLS; NVP-BEZ235; MAPK; AKT;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although chemotherapy has significantly improved the prognosis of patients with cervical cancer, many patients exhibit selective responses to chemotherapy. This study aimed to identify genes associated with the sensitivity of cervical cancer cells to paclitaxel. SiHa cells were transfected with lentiCRISPR (genome-scale CRISPR knockout library v. 2) and then treated with paclitaxel or vehicle for 14 days. Subsequently, we screened for candidate genes whose loss resulted in sensitivity to paclitaxel. We obtained 374 candidates, some of which were consistent with those reported in previous studies, including ABCC9, IL37, EIF3C, AKT1S1, and several members of the PPP gene family (PPP1R7, PPP2R5B, PPP1R7, and PPP1R11). Importantly, our findings highlighted the newly identified genes that could provide novel insights into the mechanisms of paclitaxel sensitivity in cervical cancer. Cas9 technology provides a reliable method for the exploration of more effective combination chemotherapies for patients at the gene level.
引用
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页码:1972 / 1978
页数:7
相关论文
共 39 条
  • [1] Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-κB and the serine/threonine kinase Akt and is independent of tubulin polymerization
    Bava, SV
    Puliappadamba, VT
    Deepti, A
    Nair, A
    Karunagaran, D
    Anto, RJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (08) : 6301 - 6308
  • [2] Cohen PTW, 2002, J CELL SCI, V115, P241
  • [3] Multiplex Genome Engineering Using CRISPR/Cas Systems
    Cong, Le
    Ran, F. Ann
    Cox, David
    Lin, Shuailiang
    Barretto, Robert
    Habib, Naomi
    Hsu, Patrick D.
    Wu, Xuebing
    Jiang, Wenyan
    Marraffini, Luciano A.
    Zhang, Feng
    [J]. SCIENCE, 2013, 339 (6121) : 819 - 823
  • [4] Giannios J, 2007, DRUG CHEM TOXICOL, P1
  • [5] BIOCHEMISTRY OF MULTIDRUG-RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTER
    GOTTESMAN, MM
    PASTAN, I
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1993, 62 : 385 - 427
  • [6] Measuring error rates in genomic perturbation screens: gold standards for human functional genomics
    Hart, Traver
    Brown, Kevin R.
    Sircoulomb, Fabrice
    Rottapel, Robert
    Moffat, Jason
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2014, 10 (07)
  • [7] Demethylation of HIN-1 reverses paclitaxel-resistance of ovarian clear cell carcinoma through the AKT-mTOR signaling pathway
    Ho, Chih-Ming
    Huang, Chi-Jung
    Huang, Shih-Hung
    Chang, Shwu-Fen
    Cheng, Wen-Fang
    [J]. BMC CANCER, 2015, 15
  • [8] Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells
    Huang, Y
    Ray, S
    Reed, JC
    Ibrado, AM
    Tang, C
    Nawabi, A
    Bhalla, K
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 1997, 42 (01) : 73 - 81
  • [9] Dysregulation of the TSC-mTOR pathway in human disease
    Inoki, K
    Corradetti, MN
    Guan, KL
    [J]. NATURE GENETICS, 2005, 37 (01) : 19 - 24
  • [10] Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo:: evidence for augmentation of a 42-specific γ secretase
    Jankowsky, JL
    Fadale, DJ
    Anderson, J
    Xu, GM
    Gonzales, V
    Jenkins, NA
    Copeland, NG
    Lee, MK
    Younkin, LH
    Wagner, SL
    Younkin, SG
    Borchelt, DR
    [J]. HUMAN MOLECULAR GENETICS, 2004, 13 (02) : 159 - 170