The roles of miRNAs in human breast cancer and canine mammary tumor

Yu, Richard Ming Chuan; Cheah, Yoke Kqueen

doi:10.1186/s41241-017-0043-7

Applied Cancer Research

Table 1 miRNAs expression level, their targets, functional roles and potentials as biomarker in human breast cancer (female)

From: The roles of miRNAs in human breast cancer and canine mammary tumor

miRNA Human (Female)	Sample Source	Expression Level	Target	Functional Role, Biomarker as Diagnostic, Prognostic, Therapeutic	Authors, year of publication
Let 7 family	Cell line, Tissue, Blood, Serum	Down	RAS, HMGA2, H-RAS, KRAS, MYC, CCND2, PBX3, LIN28, PEBP1, BMI-1	Proliferation, differentiation, self-renewal, EMT, Tamoxifen response, diagnostic and prognostic biomarker	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3] Schooneveld et al. 2015 [36], Kaboli et al. 2015 [58], Takahashi et al. 2015 [59], Zhang et al. 2014 [60], Schwarzenbacher et al. 2013 [61], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
7	Tissue	Down	FAK, IGFR, EGFR, REGγ	Regulating gene expression, cell growth and survival control, Tamoxifen response, Docetaxel and Cisplatin sensitive, diagnostic biomarker	Bertoli et al., 2015 [3], Kaboli et al. 2015 [58]
9	ER+ tissue, Cell line	Up	CCND1, E-CAD, CDH1	Regulate CDKs and control cell cycle progression G1 to S, cellular adhesion and metastasis, diagnostic and prognostic biomarker	Bertoli et al., 2015 [3], Kaboli et al. 2015 [58], Schooneveld et al. 2015 [36], Zhang et al. 2014 [60]
10b	Cell line, Tissue	Up	HOXD 10, SYNDECAN-1, TIAM1, E-CAD, RHOC	Promote cell migration, invasion, metastasis, EMT, stemness of BCSC, Tamoxifen resistance, diagnostic biomarker	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36] Kaboli et al. 2015 [58], Takahashi et al. 2015 [59], Shafi et al. 2014 [32], Zhang et al. 2014 [60], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
16	Plasma, Tissue, Cell line, Serum	Down	WIP1, BCL2, E2F, CDK6, CCND1	Regulate cell proliferation and death, diagnostic and prognostic, Doxorubicin and Docetaxel response	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Zhang et al. 2014 [60], Schwarzenbacher et al. 2013 [61],
17-5p	Tissue	Down	E2F1, CCND1, AIB1	Regulate CDKs and control cell cycle progression G1 to S, cancer cell proliferation, diagnostic biomarker	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
17/92	Cell line	Up	E2Fs, ERα, C-MYC, AIB1, CYCLIN D1, MEKK2	Control cell cycle, proliferation, tumorigenesis, proapoptosis, metastasis	Kaboli et al. 2015 [58], Schooneveld et al. 2015 [36], Xiang et al. 2010 [63], Bonauer et al. 2009 [64]
21	Plasma/Tissue/Cell line, Serum, Blood	Up	PTEN, BCL-2, TPM1, TIMP3, HER, PDCD4, MASPIN, CDC25, PTEN, BCL2, RHOB, MMPs, HIF1A	Promote cell migration, invasion, metastasis, EMT, diagnostic and prognostic biomarkers, resistant to Cisplatin, Doxorubicin, Topotecan	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Schoonevel et al. 2015 [36], Kodahl et al.2014 [65], Shafi et al. 2014 [32], Zhang et al. 2014 [60]
22	Cell line	Down	CDK6. SIRT1, SP1, TET1–3, TIP60	Regulator of cellular senescence, inhibit tumor growth and metastasis, regulate EMT genes by repressing TIP60, prognostic biomarker (TIP60/miR-22)	Kaboli et al. 2015 [58], Takahashi et al. 2015 [59], Schwarzenbacher et al. 2013 [61]
27a	Tissue	Up	FOXO1, ZBTB10/RINZF, MYT-1, ZBTB10	Cell cycle progression G2 to M check point regulation, tumor development, invasion and metastasis, diagnostic and prognostic biomarker	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Zhang et al. 2014 [60], Tang et al. 2012 [66], Fu et al. 2011 [62], Mertens-Talcott et al. 2007 [67]
27b	TNBC, Cell line and tissue	Up	CYP1B1, ARFGEF1, FOXO1, PPARγ, ST14, NISCH	Regulate cell cycle progression, proliferation, metastasis, angiogenesis, drug resistance, generation of breast cancer stem cells (BCSCs), prognostic biomarker	Ding et al. 2017 [68], Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Zhang et al. 2014 [60], Schoonevel et al. 2015 [36], Fu et al. 2011 [62]
29b	Tissue	Down	ITGB1, MMP2, TIAM1, VEGFA, ANGPTL4, LOX	Inhibit proliferation, angiogenesis and metastasis. Diagnostic biomarker	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3]
30	TNBC, Cell line and BCSCs	Down	UBC9, ITGB3, AVEN	Regulate self-renewal and antiapoptotic, in-vitro mammosphere formation.	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58] Schwarzenbacher et al. 2013 [61]
30c	Tissue	Down	TWF1, IL-11, VIM	Tamoxifen response, suppresses interleukin 11 expression and inhibit resistance to paclitaxel and doxorubicin	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Takahashi et al. 2015 [59]
31	BC and TNBC cell line	Down	RHOA, RDX, ITGA5, FZD3, M-RIP, MMP16, WAVE3, PKCepilon	Inhibits several steps of the invasion-metastasis cascade in breast cancer	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Schooneveld et al. 2015 [36], Zhang et al. 2014 [60], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
34a, b, c	BC and TNBC cell line, Tissue	Down	NOTCH4, NOTCH 1, CCND1, AXL, WIP1 C-MYC, FRA1, CDK4, CDK6, SIRT1, E2F3	Cell Cycle control, invasion and metastasis, EMT, self-renewal and EMT, diagnostic biomarker, radiotherapy sensitive	Bertoli et al. 2015 [3], Zhang et al. 2014 [60], Schwarzenbacher et al. 2013 [61] Kaboli et al. 2015 [58], Fu et al. 2011 [62] O′ Day et al. 2010 [2]
125a-5p	Cell line, Tissue	Down	HDAC4, HDAC5, HER3, HUR	Inhibit cell proliferation and differentiation, induce apoptosis, Docetaxel sensitive, diagnostic biomarker	Hsieh et al. 2015 [69], Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Zhang et al. 2014 [60]
125b	Cell line, Tissue	Down	HER2, EST1, E2F3, EPO, EPOR, ENPEP, CK2-α, CCNJ, MEGF9, ERBB2, HUR, BAK	Inhibit cell proliferation and differentiation, diagnostic biomarker, FEC chemotherapy resistant, Taxol resistant, Trastuzumab sensitive.	Kurozumi et al. 2016 [57], Bertoli et al., 2015 [3], Schooneveld et al. 2015 [36], Zhang et al. 2014 [60], Feliciano et al. 2013 [70], Wang et al. 2012 [71]
126	BC and TNBC cell line, Tissue	Down	IGFBP2, PITPNC1, MERTK, VEGF, IRS-1, PIK3R2	Cell cycle progression from G1/G0 to S, reduces metastasis and angiogenesis, diagnostic biomarker	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Zhang et al.2014 [60], Fu et al. 2011 [62]
128	Cell line and BCSCs	Down	BMI-1, ABCC5	Regulate cell cycle, inhibit tumor growth and angiogenesis, Doxorubicin sensitive	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Schwarzenbacher et al. 2013 [61]
143	Serum	Down	HER3	Inhibit cell invasion and metastasis, diagnostic biomarker	Schooneveld et al. 2015 [36], Kaboli et al. 2015 [58], Kodahl et al. 2014 [65]
145	Serum/Plasma/Tissue, Cell line	Down	EGF, C-MYC, VEGF, N-CADHERIN, HIF-2α, MUCIN1, HER3, IRS1, RTKN	Inhibit cell invasion and metastasis, diagnostic biomarker	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Zhang et al. 2014 [60], Kodahl et al. 2014 [65] Fu et al. 2011 [62]
146	BC and TNBC cell line, Tissue	Down	BRCA1, NFκB, TRAF6, IRAK1, ROCK1, CXCR4, EGFR	Proliferation, antiapoptotic, diagnostic biomarker	Bertoli et al. 2015 [3], Shafi et al. 2014 [32]
146a	BC and TNBC cell line, Tissue	Down	ICAM1, VHRF1, NF-Κb, EGFR	Antimetastasis, symmetric and asymmetric division of CSCs	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3], Kaboli et al. 2015 [58]
146b	BC and TNBC cell line, Tissue	Down	ICAM1, VHRF1, NF-κB, STAT3, EGFR	Anti-metastasis	Kurozumi et al. 2016 [57], Schooneveld et al. 2015 [36], Kaboli et al. 2015 [58]
155	Serum, Heterogenous BC, Tissue	Up	CXCR4, FOXO3, TRF1, SHIP, TP53INPI, RHOA, SOCS1	Cell growth, proliferation, metastasis, telomere synthesis, TGF- β Signaling, diagnostic and prognostic biomarker, Taxane response	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Kodahl et al.2014 [65], Zhang et al. 2014 [60], Kaboli et al. 2015 [58], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
181	Cell line and BCSCs, Serum	Up	ATM	Regulate in vitro mammosphere formation, anti-apoptotic	Bertoli et al. 2015 [3], Schwarzenbacher et al. 2013 [61], Kaboli et al. 2015 [58]
181b	Tissue, Blood, Cell line	Up	SMAD3, BIM, CDK8	Promotes cell proliferation, migration and metastasis, associated with the resistance to Doxorubicin, diagnostic biomarker	Zheng et al. 2015 [72], Kaboli et al. 2015 [58]
182	Cell line and tissue	Up	BRCA1, FOXO1	Proliferation, antiapoptotic, Tamoxifen response	Kurozumi et al. 2016 [57], Bertoli et al. 2015 [3] Kaboli et al. 2015 [58], Zhang et al. 2014 [60]
194	Tissue	Up	TLN2, CDH2, RAC1, THBS1, ITGA9	Antimetastastic, inhibit cell migration, enhance chemosensitivity, associate with trastuzumab (Herceptin) response, diagnostic biomarker.	Bertoli et al., 2015 [3], Kaboli et al. 2015 [58], Calura et al. 2014 [73], Le et al. 2012 [74]
199b-5p	Tissue, Cell line	Down	HER2	Regulate proliferation, invasion and metastasis, prognostic biomarker	Fang et al. 2016 & 2013 [75, 76]
200	Tissue and Cell line	Down	BMI-1, SUZ12, ZEB1, ZEB2, PLCG1, TGFβ2, FAP-1, SNAI-1, SNAI-2, CTNNB1	Reduces tumor growth, anti-metastatic, stemness and EMT.	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Shafi et al. 2014 [32], Hilmarsdottir et al. 2014 [77], Schwarzenbacher et al. 2013 [61], O′ Day et al. 2010 [2]
200a	Tissue and Cell line	Down	SLUG, BMI1, ZEB1, ZEB2, EPHA2	Reduces tumor growth, anti-metastatic	Tsouko et al. 2015 [78], Bertoli et al. 2015 [3], Kaboli et al. 2015 [58]
200b	Tissue and Cell line	Down	SP1, RAB21, RAB23, RAB18, RAB3B	Control cell proliferation and apoptosis, Prognostic biomarker	Yao et al. 2015 [79], Ye et al. 2014 [80]
200c	Tissue and cell line	Down	BMI1, ZEB1, ZEB2, FHOD1, PPM1F	Reduces tumor growth, antimetastatic, inhibit clonogenicity of BCSCs, induce differentiation, sensitize breast cancer cells to doxorubicin, therapeutic biomarker	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58], Zhang et al. 2014 [60], Jurmeister et al. 2012 [81], Fu et al. 2011 [62], Shimono et al. 2009 [82]
204	Tissue and cell line	Down	JAK2, ZEB2, FOXA1, BDNF, IL-11, PDEF, SIX1, SAM68	Inhibit cell growth, invasion and metastasis, induce cell apoptosis, suppress BCSCs, diagnostic and prognostic biomarker, Tamoxifen response	Shen et al. 2017 [83], Li et al. 2016 [84], Flores-Pérez et al. 2016 [85], Bertoli et al. 2015 [3]
205	Ductal BC,BC and TNBC cell line	Down	HER3, E2F, P53, ZEB-1, HMGB3, VEGF-A, BRBB3	Inhibit proliferation, invasion and EMT, prognostic biomarker	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Takahashi et al. 2015 [59], Zhang et al.2014 [60], Fu et al. 2011 [62]
206	BC and TNBC cell line	Down	ERα, CCND2, ESR1, NOTCH3, SRC-1, SRC-3, GATA-3, ERα, Cx43	Reduces migration, invasion and anti-metastatic	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Kaboli et al. 2015 [58], Shafi et al. 2014 [32], Zhang et al. 2014 [60], Fu et al. 2011 [62], O′ Day et al. 2010 [2]
210	IDC, Cell line, Tissue, Plasma	Up	E2F3, NPTX1, RAD52, ACVR1B, MNT, CASP8AP2, FGFRL1, HOXA-1, HOXA-9	Prognostic and diagnostic biomarker, Herceptin resistance	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Devlin et al. 2011 [86], Huang et al. 2010 [87]
216b	Tissue and cell line	Down	SDCBP, P2X7	Suppress breast cancer growth and metastasis, proapoptoic, therapeutic biomarker	Jana et al. 2016 [88], Kaboli et al. 2015 [58], Zheng et al. 2014 [60]
222	Serum, Tissue	Up	ABCG2, MMP1, SOD2, TIMP3, GNAI3	Inhibit migration and invasion, enhance breast cancer cells to cisplatin responsiveness, diagnostic and prognostic biomarker	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Zhao et al. 2015 [89], Kodahl et al. 2014 [65]
221/222	Cell line	Up	ERα, P27kip1, KIT, P57, PTEN	Tamoxifen resistant luminal type breast cancer and Fulvestrant resistant	Bertoli et al. 2015 [3], Takahashi et al. 2015 [59] Piva et al. 2013 [30], Fu et al. 2011 [62]
224	Tissue and Cell line	Up	CXCR4, CDC42, RKIP, FZD5, FZD4,	Inhibited cell proliferation and migration	Liu et al. 2014 [90], Zhang et al.2014 [60]
335	Cell line, Tissue	Down	SOX4, SPL, BCL-W, SOX4, TNC, PTPRN2, MERTK, RSP1, IGF1, ID4, ERα	Suppress metastasis and migration, proapoptotic, diagnostic and prognostic biomarkers	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36] Kaboli et al. 2015 [58], Shafi et al. 2014 [32], Zhang et al. 2014 [60]
339-5p	Tissue	Down	BCL6	Proapoptotic, Tamoxifen response	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58]
342-5p	Heterogenous BC, Tissue	Down	EGRF, HER2, AKT, PKC, ESR1, ERN2, PELP1, SRC	Regulate cell cycle, antiproliferative, diagnostic and prognostic biomarker, regulate Tamoxifen response	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36] Kaboli et al. 2015 [58], Leivonen et al. 2014 [91], Romero-Cordoba et al. 2012 [92]
373	Cell line	Up	CD44	Cell migration, invasion and metastasis	Bertoli et al. 2015 [3], Schooneveld et al. 2015 [36], Shafi et al. 2014 [32], Fu et al. 2011 [62]
429	Cell line, Tissue	Down	ZEB1, ZEB2, CRKL, TUBB2A, TGF-β, XIAP	Anti-proliferative and anti-metastatic, member of miR-200 family	Takahashi et al. 2015 [59], Ye et al. 2015 [93], Kaboli et al. 2015 [58], Wang et al. 2015 [94]
491-5p	Cell line, Tissue	Down	EGRF, HER2, NNAT, JMJD2B	Antiproliferative, antimetastatic especially estrogen stimulated breast cancer cells	Hui et al. 2015 [95], Kaboli et al. 2015 [58]
495	Cell line, BCSCs	Up	REDDI, ECAD	Increased tumor formation, downregulation of E-cadherin, maintaining a stem-cell line phenotype	Kaboli et al. 2015 [58], Schwarzenbacher et al. 2013 [61]
520c	Cell line, Tissue	Up	CD44	Cell migration, invasion and metastasis, Tamoxifen response	Bertoli et al. 2015 [3], Kaboli et al. 2015 [58]
708	Tissue, Cell line	Down	NNAT	Anti-proliferative and anti-metastatic	Kurozumi et al. 2016 [57], Kaboli et al. 2015 [58], Ryu et al. 2013 [96]

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