Table 1.

SOX9 Targeting miRNAs in Human Breast Cancer

miRNA	Patient samples	In-vitro model	In-vivo model	Functions	Refs
miR-140	43 tumor samples and 5 normal samples	MCF10A, MCF10DCIS, SUM225CWN and SUM102PT cells	Immuno-deficient nude female mice	miR-140 is significantly downregulated in cancer stem-like cells and enforced expression reduced CSC self-renewal and tumor formation by directly targeting ALDH1 and SOX9	[47]
miR-3134		MCF7 cells		miR-3134 (ARE binding miRNA) induced the expression of SOX9 in collaboration with ARE binding protein HuR	[91]
miR-140		MCF10DCIS and mouse preadipocytes (3T3L1, MBA1)	Immuno-deficient Nu/Nu female mice	miRNA-140 was upregulated after shikonin treatment and reduced the expression of SOX9	[92]
miR-206	40 tumor samples	MCF7, MDA-MB361, MDA-MB231, MDA-MB435, and HCC1395		miR-206 expression was downregulated in TNBC. Ectopic expression of miR-206 inhibited cell invasion and angiogenesis of TNBC by downregulating the expression of VEGF, MAPK3, and SOX9	[14]
miR-155		MCF7 and MDA-MB231		miR-155 was induced in exosomes isolated from CSCs and resistant cells and that exosomes induced the expression of SOX9	[93]
miR-133b	38 paired tissues	BT549, MDA-MB231, BT474, SKBR3, HCC1937	BALB/c female nude mice, SCID/beige mice	miR-133b was downregulated in tumor and associated with advanced grade. Forced expression of miR-133b inhibited cell growth, invasion both in-vitro and in-vivo by directly modulating SOX9	[94]
miR-511	51 pair	MDA-MB231, MCF7	BALB/C nude mice	miR-511 was downregulated in BC tissues and cell lines and associated with lymph node metastasis and tumor stage. Ectopic expression inhibited cell growth and metastasis invite and also attenuated tumor growth in-vivo by directly targeting SOX9 mediated PI3K/Akt pathway	[95]
miR-190	30 paired tissues	T47D, MCF7, MDA-MB231, MDA-MB435, MDA-MB468	Female BALB/c nude mice	miR-190 induced TAM sensitivity of BC cells both in-vitro and in-vivo by targeting SOX9 resulted introverted Wnt/β-catenin signaling. The expression of miR-190 inversely correlated with SOX9 in BC samples	[96]
miR-9-5p, miR-195-5p, and miR-203a-3p	12 pre and post NT	MDA-MB231, MCF7, BT474	NOD/SCID/IL2R γ-null (NSG) mice	Chemotherapy induced EV miRNA which targeted ONECUT2 resulting induction of CSC phenotype through induction of NOTCH1, SOX9, NANOG, OCT4, and SOX2	[97]
miRNA-215-5p	39 pair of breast carcinoma tissues	MCF10A, MDA-MB468, MDA-MB231 and MCF7	BALB/c nude mice	miR-215-5p was downregulated in BC tissue samples. Upregulation of miR-215-5p inhibited BC cells growth and metastasis both in-vitro and in-vivo by directly targeting SOX9	[98]

BC, breast cancer; TNBC, triple negative BC; NT, neoadjuvant therapy