SLUG and SOX9 Cooperatively Regulate Tumor Initiating Niche Factors in Breast Cancer

Fazilaty, Hassan; Gardaneh, Mossa; Akbari, Parvin; Zekri, Ali; Behnam, Babak

doi:10.1007/s12307-015-0176-8

Cited by 32 publications

(28 citation statements)

References 14 publications

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“…Breast cancer patients with high expression of SOX9 exhibited shorter overall survival than those with low expression (22,23). Numerous other studies have supported the importance of SOX9 in breast cancer occurrence and development through the regulation of multiple biological behaviors (24)(25)(26)(27)(28). In the current study, it was demonstrated that miR-511 targets SOX9 to inhibit the malignant progression of breast cancer via the PI3K/ Akt pathway.…”

Section: Discussionsupporting

confidence: 57%

“…In this study, it was aimed to determine the expression of miR-511 in breast cancer, test its role in malignant progression and explore downstream targets. SRY-box 9 (SOX9) was predicted as a potential target of miR-511 and was chosen for further investigation as this gene was previously reported to be upregulated in breast cancer and implicated in breast carcinogenesis and development (22)(23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

et al. 2018

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Numerous studies have revealed that a subset of microRNAs (miRNAs) is aberrantly expressed in breast cancer. The dysregulation of miRNAs is involved in the tumorigenesis and progression of breast cancer due to their negative regulation of downstream target genes. Therefore, the identification of deregulated miRNAs in breast cancer may provide important insights into the diagnosis and treatment of patients with this disease. miRNA-511 (miR-511) has been identified to be deregulated in diverse human cancer types; however, neither the expression status nor the detailed roles of miR-511 in breast cancer have been clarified. Thus, it was aimed to determine the expression of miR-511 in breast cancer, examine the role in malignant progression and explore its downstream targets. The results of the present study revealed that the expression of miR-511 was downregulated in breast cancer tissues and cell lines. Decreased expression of miR-511 was significantly associated with lymph node metastasis and tumor stage in patients with breast cancer. Functional analyses revealed that restoring miR-511 expression suppressed breast cancer cell proliferation and colony formation, promoted apoptosis and reduced metastasis in vitro, while it attenuated tumor growth in vivo. Additionally, it was revealed that SRY-box 9 (SOX9) was a direct target gene of miR-511 in breast cancer cells. SOX9 was upregulated in breast cancer tissues and its expression was inversely correlated with that of miR-511. Furthermore, SOX9 inhibition simulated the tumor-suppressive roles of miR-511 overexpression in breast cancer cells, while SOX9 reintroduction partially rescued these effects of miR-511. Notably, the upregulation of miR-511 targeted SOX9 to deactivate the PI3K/Akt signaling in breast cancer in vitro and in vivo. In conclusion, miR-511 was downregulated in breast cancer, and impeded its malignant progression by directly targeting SOX9 and regulating the PI3K/Akt pathway. Thus, miR-511 is a potential therapeutic target in breast cancer.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

et al. 2018

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“…In the present study, we constructed an miRNA–mRNA interaction network to obtain an overview of the putative function of the most differentially expressed miRNAs. This miRNA–mRNA interaction network suggested that differentially expressed miRNAs regulate tumor growth and metastasis‐related genes such as EGFR, MET, SOX9, SP1, PTEN, FOXO1 and ZEB1 . Of these target genes, SP1 and ZEB1 showed the most linkage with differentially expressed miRNAs.…”

Section: Discussionmentioning

confidence: 88%

Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy

Sun

Zhong

Wei

et al. 2019

The Journal of Gene Medicine

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Background Sentinel lymph node (SLN) property assessment (with or without metastasis) is important when deciding the surgery for breast cancer; however, the current diagnosis of SLN metastasis remains to be studied. microRNAs (miRNAs) have been confirmed previously as a molecular marker for the diagnosis, development and prognosis of tumors. However, the detailed role of miRNAs in the diagnosis of SLN metastasis has not been reported. Methods The present study aimed to explore the potential use of miRNAs in the diagnosis of SLN using RNA sequencing (RNA‐seq) and a quantitative real‐time polymerase chain reaction (qRT‐PCR) to compare the expression profiles of miRNAs in patients with breast cancer with or without SLN metastasis. Results The RNA‐seq results revealed that 1993 miRNAs were differentially expressed in patients with breast cancer with SLN metastasis. Among these miRNAs, 1960 were up‐regulated and 33 were down‐regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that these differentially expressed miRNAs were associated with tumor growth and metastasis and were also predicted to regulate a series of tumorigenesis and metastasis genes. In particular, the most differentially expressed miRNAs were validated by qRT‐PCR, such that miR‐200a‐3p and miR‐96‐5p were up‐regulated and miR‐1‐3p and miR‐486‐3p were down‐regulated in patients with breast cancer with SLN metastasis. Conclusions The findings of the present study suggest that there is an association of miRNAs with SLN metastasis and also that miRNAs function as biomarkers with respect to the choice of therapy and disease prognosis.

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“…Moreover, SOX9 is known to promote epithelial-mesenchymal transition (EMT) together with SLUG ( 32 , 33 ), one of the key transcriptional factors in EMT ( 34 ). When SOX9 and SLUG were overexpressed in breast cancer cells, they cooperatively facilitated EMT, resulting in elevated tumorigenesis and metastasis ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma

et al. 2018

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Transcription factor SRY-box 9 (SOX9) is a key regulator of chondrocyte differentiation and sex determination, and it is also involved in the progression of various types of human cancer. However, its putative association with oral squamous cell carcinoma (OSCC) remains elusive. The aim of the present study was to investigate the expression profiles of SOX9 in various oral epithelial lesions, including OSCC. We performed immunohistochemical analysis of SOX9 expression in surgical specimens of OSCC, which simultaneously exhibited different grades of epithelial lesions, and analyzed the correlation between SOX9 expression and several clinicopathological factors. Moreover, we performed immunofluorescent staining, western blot analysis and real-time reverse transcription-polymerase chain reaction to assess SOX9 expression in OSCC HSC-3 (a metastatic cell line) and HSC-4 (a non-metastatic cell line) cell lines. In surgical specimens, SOX9 expression was detected in the nuclei of proliferating cells in areas with epithelial dysplasia and carcinoma in situ, but not in areas with normal epithelia. Nuclear SOX9 expression was observed in most SCC cells. Notably, cytoplasmic SOX9 expression was confirmed only in some SCC cells; however, cytoplasmic SOX9 expression was significantly and positively correlated with poor clinical outcomes. Both protein and mRNA expression of SOX9 were significantly higher in the HSC-3 cell line than that in the HSC-4 line. Notably, however, only HSC-3 cells exhibited cytoplasmic localization of SOX9 expression. Our findings indicate that SOX9 may be involved in the tumorigenesis and progression of OSCC. Furthermore, its cytoplasmic expression represents a potential predictive biomarker for tumor aggressiveness and OSCC prognosis.

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SLUG and SOX9 Cooperatively Regulate Tumor Initiating Niche Factors in Breast Cancer

Cited by 32 publications

References 14 publications

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy

Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma

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