<p>MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8</p>

Abstract

The effects of miR-139 on the tumorigenicity of triple negative breast cancer (TNBC) and the underlying mechanisms were investigated. Methods: Normal human breast epithelial (MCF-10A) and TNBC cell lines (HCC1806 and BT549) were used for microRNA (miR)-139 overexpression, SOX8 overexpression, and knockdown studies as in vitro models of TNBC. The expression of SOX8 and miR-139 was detected by reverse transcription-polymerase chain reaction. CCK8 and clone formation assays were used to evaluate cell proliferation ability. Transwell assays and flow cytometry were used to test cell migration and apoptosis, respectively. Cell tumorigenicity was examined by tumor sphere formation assays. The interaction between miR-139 and SOX8 was examined by dual-luciferase reporter assays. The expression of SOX8, cleaved caspase-3, and cleaved caspase-9 was analyzed by Western blotting. The findings were validated in vivo using a nude mouse transplanted tumor model. Results: SOX8 expression was higher (P < 0.05) and miR-139 expression was lower (P < 0.05) in HCC1806 and BT549 cells than in MCF-10A cells. SOX8 overexpression significantly enhanced cell proliferation and migration, reduced the rate of cell apoptosis, and increased tumor sphere formation (P < 0.05) compared with the control group, whereas SOX8 knockdown had the opposite effect (P < 0.05). Overexpression of miR-139 markedly decreased cell proliferation and migration, increased cell apoptosis in vitro, and decreased tumor angiogenesis and volume in vivo (P < 0.05). Conclusion: miR-139 suppressed the tumorigenicity of TNBC cells by targeting SOX8.

Regulation of cancer stem cells in triple negative breast cancer

“…MiR-205 is another negative regulator of stemness in TNBC which targets ZEB1/2 and is repressed by Notch signaling [220,221] . Dong et al [222] demonstrated miR-139 suppresses tumorigenicity in TNBC by targeting CSC factor SOX8. MiR-200c also inhibits CSC-factor ZEB2 in TNBC, repressing EMT [223] .…”

“…Dong et al . [ 222 ] demonstrated miR-139 suppresses tumorigenicity in TNBC by targeting CSC factor SOX8. MiR-200c also inhibits CSC-factor ZEB2 in TNBC, repressing EMT [ 223 ] .…”

Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis

“…Dependent on m6A modification, KIAA1429 increases the stability of its downstream genes and thus elevates their expressions in cancers [15,24]. SOX8 is considered a detrimental prognostic factor for triple-negative breast cancer and tongue squamous cell cancer [19,34,35].…”

“…Dependent on m6A modification, KIAA1429 increases the stability of its downstream genes and thus elevates their expressions in cancers [ 15 , 24 ]. SOX8 is considered a detrimental prognostic factor for triple-negative breast cancer and tongue squamous cell cancer [ 19 , 34 , 35 ]. Additionally, several studies have highlighted the role of SOX8 in augmenting EMT and drug resistance in cancers [ 36–38 ].…”

Identification of MicroRNAs as Diagnostic Biomarkers for Breast Cancer Based on the Cancer Genome Atlas

“…Previous studies have shown that miR-21 overexpression in breast cancer is associated with cell proliferation, progression, metastasis, and poor prognosis [ 38 , 39 ]. It has also been reported that miR-21 promotes invasion and cell proliferation by targeting programmed cell death 4 (PDCD4) [ 38 ]; miR-139 has been reported to act as a tumor suppressor in several cancer types, such as prostate cancer, endometrial cancer, and breast cancer [ 40 , 41 , 42 ]. In addition to miR-21 and miR-139, selected DE miRNAs have also been confirmed to function as one of the major components in cancer biology by other groups.…”