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. 2021 Jan 4;12(1):17. doi: 10.1038/s41419-020-03327-7

Table 1.

miRNAs targeting Zeb1 and Zeb2.

miRNA Targets Cancer subtype Expression changes Effect References p53 regulation
miR-142-3p Zeb1 N/S Downregulated in BC. Reduced expression is associated with tumor size and lymph node metastasis 98 Downregulated by mutant p53
Attenuates breast CSC characteristics 99
miR-96-183 (miR183-96-182 cluster) Zeb1 N/S High expression is a prognostic biomarker for BC, and correlated with local relapse, distant metastasis, and poor clinical outcomes 100 Induced by p53
LA Downregulated in LA BC-induced overexpression of miR-183 inhibited migration of breast cancer cells 101
miR-96 was upregulated in BC, enhanced proliferation, migration, and tumor growth 102
miR-141 (miR-200 family)

Zeb1

Zeb2

N/S The level was significantly higher in the blood of patients with stage I–III, lymph node metastasis, and Her2 negative tumors. Low expression of miR-141 was associated with unfavorable overall survival 103 Induced by p53
TN ­ Overexpression promotes migratory and invasive ability of TN BC cells 104
TN ­ Ectopic expression enhanced brain metastatic colonization 105
N/S High level is a marker of circulating tumor cells presence and metastasis 106
miR-200a-200b-200c (miR-200 family)

Zeb1

Zeb2

TN ­ High levels block angiogenesis in tumor 107 Induced by p53
MBC High levels are associated with metaplastic breast cancer and upregulated Zeb1, Zeb2, Snail, and Slug 108
N/S High levels are markers of circulating tumor cells presence and metastasis 106
TN Low level is a characteristic of triple-negative BC subtype 109
LA, LB Low expression indicated reduced survival in PR-positive BC cases 110
HER2+, TN High expression in tumors and increased content in blood were associated with shortened relapse-free survival of patients with in PR-negative BC 103
miR-429 (miR-200 family)

Zeb1

Zeb2

TN Low level is a marker of BC compared to normal breast tissue. TN breast cancer is characterized by the lowest miR-429 compared to other BC types 111 Induced by p53
TN - Upregulated in TN BC (MDA-MB-231 and MDA-MB-468) treated with δ-tocotrienol and induces apoptosis 112
TN ­ High expression suppresses metastasis formation and migration of MDA-MB-231cells 113
miR-33a Zeb1 TN, MTC Downregulated in TN breast cancer 114 Suppresses p53 in hematopoetic stem cells
N/S Expression is negatively associated with lymph node metastasis and clinical stage, expression lower in metastatic cell lines 65
miR-655 Zeb1 TN Reduced expression in triple-negative BC compared to normal tissue and other cancer types. Lower expression is associated with higher lymph-node status 115
miR-153 Zeb2 LA, TN ­ Ectopic expression inhibited tumor growth and impair the migration and invasion of breast cancer cells 116
TN ­ Expression was induced by Mifepristone and resulted in suppressed tumor growth of the TN BC cell lines and patient-derived xenografts 117
miR-192 Zeb2 N/S Decreased in BC tissues 118 Induced by p53
N/S Decreased in BC tissues and known to inhibit proliferation 119
miR-215 Zeb2 N/S Downregulated in BC and targets Sox9 lower levels contributed to unfavorable prognosis 120 Induced by p53, activates p53
N/S Low expression correlated with higher tumor grade, Her2 positive status, lymph node metastasis, and low expression led to lower 5-year DSS (Disease-specific survival) 121
miR-218 Zeb2 N/S Lower expression of mir-218 is associated with a higher tumor grade, lymph node metastasis and poor prognosis 122
miR-338p Zeb2 N/S Downregulated in BC, expression is inversely correlated with lymph node metastasis and TNM stage 123
miR-101 Zeb1, Zeb2 MTC Downregulated in metastatic BC cells, expression varies amongst different subtypes 124 Induced by p53
miR-205 Zeb1, Zeb2 N/S Downregulated in BC 125 Induced by p53
N/S Lowest levels in basal-like and invasive TN breast cancers, inhibits CSC-like phenotype by downregulating ITGA5 126
miR-340 Zeb1, Zeb2 N/S ­ BC patients with high miR-340 expression unlikely to achieve pathologic complete response 127 Stabilizes p53
TN ­ Inhibits BC progression and metastasis 128
miR-448 Zeb1, Zeb2 N/S Downregulation is observed in BC patients with chemotherapy-induced EMT 129
miR-508-3p Zeb1, Zeb2 TN Expression was decreased in TN BC. Lower miR-508-3p expression significantly associated with lymph node metastasis and distant metastasis 130

BC breast cancer, LA luminal A subtype, LB luminal B subtype, TN triple-negative (basal-like) subtype, HER2+ HER2-positive subtype, MBC metaplastic breast cancer, MTC metastatic breast carcinomas, N/S subtype is not specified, FBT familiar breast tumors, ER estrogen receptor, PR progesterone receptor, CSC cancer stem cells.