Table 1 All of the microRNAs associated with TKIs response in lung tumor cells
From: MicroRNAs as the critical regulators of tyrosine kinase inhibitors resistance in lung tumor cells
Gene | Samples | Results | Animal study | References |
|---|---|---|---|---|
Enhancing sensitivity to TKIs | ||||
miR-1 | •  21 tumor tissues •  21 resistant tumor tissue •  PC9 and H1975 cell lines | Inhibited monocytes and lymphocyte motility by cytokines down regulations and reduced intra-tumoral CD8-positive T cells | – | Kawana [60] |
miR-1-3p | •  HCC827 and PC9 cell lines •  Xenograft model | Overcome HGF-induced Gefitinib resistance in EGFR mutant lung cancer cells by AKT/ERK inhibition | MiR-1-3p reversed HGF-induced resistance to Gefitinib in vivo | Jiao [59] |
miR-7 | •  PC-9,RPC-9, H3255, A549 and H1975 cell lines •  Xenograft model | Overcomes acquired resistance to EGFR-TKI produced by secondary mutations in EGFR-addicted cancers | MiR-7 reversed resistance to EGFR-TKI in vivo | Rai [52] |
miR-7 | •  A549 cell line | Increased the gefitinib sensitivity through inhibition of IGF1R/PI3K/Akt and EGFR/Raf1/ERK signaling pathways in NSCLC cells | – | Zhao [53] |
miR-19a | •  15 serum samples •  HCC827, H1975, A549, and PC9 cell lines •  Xenograft model | Promoted Gefitinib sensitivity by c-Met targeting in NSCLC cells | MiR-19a decreased Gefitinib resistance in xenograft model | Cao [63] |
miR-30a-5p | •  H1650, H460, and H1975 cell lines •  Xenograft model | Inhibited the PI3K/AKT signaling pathway | MiR-30a-5p increased Gefitinib sensitivity in vivo | Wang [51] |
miR-128 | •  PC9 cell line •  Xenograft model | Reversed Gefitinib resistance by reducing the CSC population by inhibiting c-met/PI3K/AKT axis | MiR-128 increased the anti-tumor effect of Gefitinib on NSCLC in xenograft model | Jiang [70] |
miR-130a | •  A549, H1975, and PC9 cell lines | Promoted Gefitinib sensitivity in NSCLC cells by Met targeting | – | Zhou [58] |
miR-133b | •  32 tumor tissue •  A549 and H1299 cell lines | Was associated with Erlotinib effectiveness | – | Bisagni [54] |
miR-138-5p | •  20 normal and tumor tissues •  PC9 and H1975 cell lines | Inhibited angiogenesis by GPR124 down regulation | – | Gao [82] |
miR-149-5p | •  A549, H1299, H1975 and, PC9 cell lines | LINC00460 sponged miR-149-5p to up regulate IL6 in lung cancer cells | – | Nakano [129] |
miR-200a | •  H3255, H1975, and HCC827 cell lines | Inhibited NSCLC cells' migration and invasion, while increased Gefitinib sensitivity | – | Zhen [31] |
miR-200c | •  150 tumor tissues •  PC9, H23, A549, H1975, H460 and H1299 cell lines | Increased Gefitinib sensitivity via ZEB1 targeting | – | Li [110] |
miR-200c | •  PC9 cell line •  Xenograft model | Increased sensitivity to Gefitinib via inhibiting the PI3K/AKT signaling pathway and cell migration by ZEB1 targeting | MiR-200c enhanced sensitivity of tumor cells to Gefitinib and induced apoptosis in xenograft model | Zhou [111] |
miR-206 | •  37 tumor and 14 normal tissues •  PC9 and HCC827 cell lines | Increased Gefitinib sensitivity by blocking the IL6/JAK1/STAT3 pathway in IL6-induced lung cancer resistance cells | – | Yang [127] |
miR-206 | •  HCC827 and PC9 cell lines •  Xenograft model | Overcome HGF-induced Gefitinib resistance in EGFR mutant lung cancer cells by AKT/ERK inhibition | MiR-1-3p reversed HGF-induced resistance to Gefitinib in vivo | Jiao [59] |
miR-206-3p | •  36 Gefitinib-resistant (GR) and 42 Gefitinib-sensitive (GS) tissues •  PC9 cell line •  Xenograft model | SNHG14 increased ABCB1 protein expression by miR-206-3p sponging, leading to NSCLC Gefitinib resistance | Silencing of SNHG14 increased sensitivity to Gefitinib in vivo | Wu [169] |
miR-223 | •  PC9 cell line •  Xenograft model | Promoted apoptosis in tumor cells by targeting the IGF1R/AKT/S6 signaling pathway and increased Erlotinib sensitivity | Combination of miR-223 and Erlotinib increased sensitivity of tumor cells | Zhao [73] |
miR-223 | •  PC9 cell line •  Xenograft model | Inhibited the IGF1R/PI3K/AKT signaling pathway and Erlotinib resistance | MiR-223 reversed resistance to Erlotinib in vivo | Han [157] |
miR-365a-5p | •  27 normal and 58 tumor tissues •  PC9 cell line •  Xenograft model | Reduced cell proliferation and Gefitinib resistance via PELI3 targeting | MiR-365a-5p significantly decreased the tumor size in xenograft model | Li [99] |
miR-483-3p | •  HCC827, H1975, A549, H292, H1299, and PC9 cell lines •  Xenograft model | Promoted Gefitinib sensitivity in NSCLC by decreasing resistant cell growth, inducing apoptosis, inhibition of invasion and migration | Silencing of miR-483-3p promoted Gefitinib resistance in EGFR-mutant NSCLC | Yue [114] |
miR-497 | •  A549 and A549/GR cell lines | Reduced IGF-1R expression and inhibited AKT1 signaling in NSCLC cells | – | Ma [72] |
miR-506-3p | •  HCC4006 cell line | Under expression of miR-506 activated the SHH pathway and induced EGFR-TKI resistance | – | Haque [172] |
miR-506-3p | •  25 normal and tumor tissues •  PC9 cell line | Gefitinib resistance via YAP1 regulation in NSCLC cells | - | Zhu [214] |
miR-608 | •  319 tumor tissues •  H1299 and PC9 cell lines | Was prognostic indicator for lung cancer during Gefitinib treatment | – | Zhang [75] |
miR-630 | •  46 tumor tissues •  PC9 and CL97 cell lines | MiR-630 down regulation promoted ERK activation through YAP1 up regulation that resulted in TKI resistance | – | Wu [215] |
miR-873 | •  PC9 cell line | MiR-873 suppression significantly promoted the proliferation of Gefitinib-treated PC9 cells, followed by GLI1 up regulation | – | Jin [175] |
miR-1262 | •  46 normal and tumor tissues •  PC9 and H1299 cell lines | MiR-1262 rs12740674 T allele was correlated with poor prognosis | – | Lei [74] |
miR-3127-5p | •  177 normal and tumor tissues •  A549 and H292 cell lines •  Xenograft model | Inhibited tumor cell growth and invasion by c-Abl targeting | miR-3127-5p decreased NSCLC tumorigenicity and metastasis in xenograft model | Sun [105] |
miR-4513 | •  319 tumor tissues •  H1299 and PC9 cell lines | miR-4513 was prognostic indicator for lung cancer during Gefitinib treatment |  | Zhang [75] |
Increasing resistance to TKIs | ||||
miR-21 | •  25 plasma samples before treatment •  25 plasma samples after treatment •  PC9 cell line •  Xenograft model | Inhibited PTEN and PDCD4 expression, while induced PI3K/AKT pathway | Suppression of miR-21 inhibited tumor progression in vivo | Li [143] |
miR-23a | •  PC9 cell line | miR-23a down regulation increased Erlotinib sensitivity of CSCs through PTEN up regulation | – | Han [144] |
miR-26a | •  5 tumor tissues •  A549, H520, SW900, H2170, and PC-9 cell lines •  Xenograft model | Promoted cell growth and TKI resistance via PTPN13 targeting | miR-26a increased Gefitinib resistance in vivo | Xu [156] |
miR-30b | 29 plasma samples before treatment 29 plasma samples after treatment | Elevated plasma levels were associated with Erlotinib's inadequate response in EGFR mutant NSCLC patients | – | Hojbjerg [152] |
miR-30c | 29 plasma samples before treatment 29 plasma samples after treatment | Elevated plasma levels were associated with Erlotinib's inadequate response in EGFR mutant NSCLC patients | – | Hojbjerg [152] |
miR-135 | •  A549, H1650, H1975, H157, and H4006 cell lines | MiR-135 suppression down regulated Bcl-2 while up regulated Bax that resulted in increased apoptosis | – | Wang [130] |
miR-135a | •  NCI-H1650 and •  NCl-H1975 cell lines | Stimulated cell proliferation, invasion, and Gefitinib resistance in NSCLC cells through RAC1 targeting | – | Zhang [160] |
miR-200c | •  HCC4006 cell line | MiR-200c/LIN28B axis plays an essential role in acquired EGFR-TKI resistance | – | Sato [113] |
miR-214 | •  7 EGFR mutant tumor tissues •  HCC827 cell line | Promoted Erlotinib resistance through LHX6 targeting | – | Liao [191] |
miR-214 | •  HCC827 cell line | Gefitinib resistance in EGFR mutant cell lines was achieved through interplay with the PTEN/AKT signaling pathway | – | Wang [142] |
miR-223 | •  HCC827 cell line •  Xenograft model | Inhibited the IGF1R/PI3K/AKT signaling pathway and Erlotinib resistance | miR-223 reversed the resistance to Erlotinib in xenograft model | Han [157] |
miR-223 | •  HCC827 cell line | Promoted the AKT and Notch signaling pathways and modulated NSCLC cell susceptibility to Erlotinib by regulating FBXW7 | – | Zhang [224] |
miR-299-3p | •  44 sensitive tumor tissues •  40 resistant tumor tissues •  A549, H1975, H1299, •  HCC827 and PC9 cell lines •  Xenograft model | RHPN1-AS1 regulated Gefitinib resistance in NSCLC by miR-299 targeting | Combination of RHPN1-AS1 and Gefitinib inhibited tumor growth in vivo | Li [205] |
miR-451 | •  A549 and H1975 cell lines •  Xenograft model | NOTCH-1 promoted Gefitinib resistance in LUAD cells through SNHG15/miR-451/ZEB1 axis in vivo and in vitro | SNHG15/miR-451/ZEB1 axis induced Gefitinib resistance in xenograft model | Huang [223] |
miR-641 | •  18 T tissues •  18 resistant T tissues •  PC9 cell line •  Xenograft model | Promoted Erlotinib resistance in NSCLC cells by NF1 targeting | Combination of miR-641 and Erlotinib increased apoptosis and decreased tumor cells proliferation in vivo | Chen [94] |
miR-762 | •  59 tumor tissues •  A549, NCI-H820, NCI-H2170, NCI-H1650, NCI-H1993, NCI-H2126, NCI-H1975, NCIH1299, NCI-H1648, NCI-H1703, NCI-H2347 and PC9 cell lines •  Xenograft model | Gefitinib resistance in NSCLC cells by mediating the IL6/STAT3 pathway | miR-762 promoted Gefitinib resistance and increased tumor formation in a xenograft model | Ge [128] |