TABLE 3.
The in vitro and in vivo roles of CRISPR/Cas9 in the management of different cancer types
| Cancer type | Cell line | Gene | Target choice | CRISPR effect and mechanism | Reference |
|---|---|---|---|---|---|
| Liver cancer | H2.35 | PTEN, p53 | C57‐HBV | Loss‐of‐function alterations of p53 and PTEN genes in H235 cells, Akt phosphorylation that resulted in corresponding somatic dysfunction and lipid accumulation | [198] |
| ‐ | PTEN and p53 (TP53 and Trp53) | β‐catenin | Knockout of both alleles results in Akt phosphorylation | [199] | |
| CD44‐C3A‐iCSCs DO clone and CD44‐C3A‐iCSCs C10 clone | Oct4, Sox2, NANOG | CD44 | Knockout CD44 to reduce cell proliferation | [200] | |
| Embryonic liver progenitor cells | p53 | HMGA2 (Nf1, Plxnb1, Flrt2, and B9d1) | Knockout both alleles to reduce the mitogen‐activated protein kinase | [201] | |
| AAV9‐HS‐CRM8‐TTRmin‐Cas9, AAV9‐U6‐mF9‐Exon1‐gRNA | F9 | Factor IX (F9) | Loss of FIX activity that induces a dsDNA break in a DNA sequence‐specific manner | [202] | |
| Lung cancer | T cells | Immune checkpoint genes | PD‐1 | Knockout the PD‐1 gene to effectively target exon 2 of the PD‐1 gene and reduce lung cancer size | [203] |
| HEK293T | Trp53, Rb1, Rosa26 | p107 and p130 | Loss of tumor suppressor genes (p107 and p130) to induce metastasis and cell proliferation | [204] | |
| NCI‐H1975, NCI‐H1650 | EGFR | EGFR | Knockout EGFR to inhibit cell proliferation and EGFR expression in lung cancer | [205] | |
| A549, NCI‐H460 | PTEM | PTEN | Knockout of both alleles of PTEN by CRISPR/Cas9 KO PTEN in slug/snail lung tumor which contributes to EMT by nuclear translocation of β‐catenin | [206] | |
| Breast cancer | Cal‐51 | MASTL | PP2A‐B55 | Knockout both alleles to inhibit cell proliferation and tumor suppression | [207] |
| MCF‐7 cells | miR‐23b | miR‐23b, miR27‐b | Knockout niR‐23b and miR27‐b genes to inhibit proliferation, and migration, of miR27‐b‐depleted cells | [208] | |
| MDA‐MB‐231, MDA‐MB‐436 | BRCA1 | BRCAI wild‐type, BRCA1m | Knockout PARPI that results in apoptosis | [209] | |
| MDA‐MB‐231, MCF‐7/TamR‐1 | Sox reductase | Sox2, Sox9 | Knockout of Sox9 reductase promote Wnt signaling and reduce tumor cell invasion | [210] | |
| ‐ | P53, PTEN, RB1, NF1 | Nutlin‐3a | Knockout PTEN, NH, P53, and RBI genes to induce cellular senescence and cell proliferation | [211] | |
| MDA‐MB‐231 | CXCR4, CXCR7 | TNBC | Knockout of the CXCR4 or CXCR7 gene that results in delay in conversion of the G1/S cycle, inhibits cell proliferation, invasion, and mitigation | [212] | |
| MCF‐I0A, HCC1806 | APOBEC3G | APOBEC3G | Knockout both alleles of APOBEC3 to inhibit cell proliferation | [94] | |
| Prostate cancer | ΔPTEN, 2924 V, PSA | ΔPTEN, 2924 V, PSA | PTEN | Knockout PTEN by CRISPR/Ca9 in ΔPTEN cell line to check the role of PTEN in prostate cancer | [213] |
| PC‐3, LNCap, DU145, | GPRC6A | GPRC6A | Activation of GPRC6A that block ERK, mTOR, and AkT phosphorylation and inhibit cell proliferation | [188] | |
| LNCaP | AR | AR | Inhibition of AR that induce apoptosis and inhibit cell proliferation | [214] | |
| PC3, DU145, 293FT | PGC1α | ERRa, PGC‐1α | Knockout ERRa and inhibit MYC levels to suppress metastasis and invasion of lung cancer growth | [215] | |
| DU 145 | NANOG, NANOGP8 | NANOG, NANOGP8 | Knockout NANOG and NANOGP8 to inhibit cell proliferation and migration, and promote drug sensitivity | [216] | |
| PC‐3 (CRL‐1435 and ATCC) | PC‐3 | TP53 | Knockout of both alleles of TP53 to induce apoptosis and inhibit cell proliferation | [217] | |
| Colorectal cancer | SW‐480 CRC cells | Mutant KRAS | KRAS | Knockout both alleles to induce apoptosis, suppress cell proliferation, and promote tumor cell death | [197] |
| CaCO‐2 | Par3L | Par3L | Knockout both alleles to induce apoptosis and inhibit cell proliferation | [196] | |
| MC‐38 | FUT | Fut4 and Fut9 | Inhibit glycosylation by the CRISPR‐dCas9‐VPR system, and activate the Fut4 and Fut9 genes to induce the neo‐expression | [194] | |
| 293T | HPV16 E6 and E7 | HPV16 | Knockout oncogenes (E6 and E7) and inhibit the expression of HPV16 E6 and E7 genes to reduce anal tumor | [195] |
“‐” refers to: not reported.
Abbreviations: PTEN, Phosphatase and tensin homolog; p53, tumor suppressor protein; C57‐HBV, hepatitis B virus transgenic mice line C57; Akt, serine threonine protein kinase; TP53, tumor protein 53; Trp53, tryptophan 53; CD, cluster of differentiation; iCSCs, induced cancer stem‐like cells; HMGA2, high mobility group A2; Plxnb1, plexin b1; Flrt2, fibronectin leucine rich transmembrane protein 2; B9d1, B9 domain containing 1; AAV, adeno‐associated virus; gRNA, guide RNA; F9, factor 9, FIX, human factor IX gene; PD‐1, programmed cell death ligand‐1; Rb1, retinoblastoma1; Rosa26, reverse orientation splice acceptor; NCI‐H1975, non‐small cell lung cancer cell line; EGFR, epidermal growth factor receptor; NCI‐H460, non‐small‐cell lung cancer cell line; PTEN, phosphatase and tensin homolog; EMT, epithelial‐mesenchymal transition; PP2A‐B55, protein phosphatase 2A having B55 substrate; MCF7, Michigan Cancer Foundation‐7 (epithelial cell line); MDA‐MB‐231, epithelial breast cancer cell line type 231; MDA‐MB‐436, epithelial breast cancer cell line type 436; BRCAI, breast cancer gene‐1; PARPI, poly(ADP‐ribose)polymerase inhibitor; MCF‐7/TamR‐1, tamoxifen‐resistant cell line derived from the MCF‐7/S0.5 human breast cancer cell line; Sox2, (sex determining region Y)‐box 2; Wnt, wingless and Int‐1 (group of signal transduction pathways); CXCR4, chemokine receptor type 4; G1/S, growth 1/synthesis phase; MCF‐I0A, noncancer human mammary cell line; HCC1806, epithelial cancer cell line; APOBEC3G, apolipoprotein B mRNA editing enzyme, catalytic subunit 3G; LNCap, lymph node carcinoma of the prostate; DU145, human prostate cancer cell line; GPRC6A, G protein‐coupled receptor class C; ERK, extracellular signal‐regulated kinase; mTOR, mammalian target of rapamycin; AR, androgen receptor; PC3, human prostate cancer cell line; 293FT, human embroyoic kidney cell line; ERRa, estrogen related receptor α; PGC1α, peroxisome‐proliferator‐activated receptor gamma co‐activator 1α; MYC, proto‐oncogene; NANOG, (Nanog homeobox) protein coding gene; ATCC, American type culture collection; TP53, tumor protein 53 gene; SW‐480 CRC cells, colorectal cancer cell line; KRAS, Kirsten rat sarcoma virus gene; CaCO‐2, human colorecta adenocarcinoma cell line; Par3L, partitioning defective 3‐like protein; MC‐38, murine colon adenocarcinoma cell line; Fut4, fucosyl transferase 4 protein coding gene; HPV16, human papilloma virus 16.