Six1 expression is associated with a poor prognosis in patients with glioma

Zhang, Xiaojun; Xu, Ran

doi:10.3892/ol.2017.5577

Cited by 15 publications

(8 citation statements)

References 42 publications

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“…Similarly, Lerbs, et al20 indicated that SIX1 could be a stem cell marker and promote cell metastasis in pancreatic cancer. Additionally, SIX1 was deemed a prognostic factor predictive of poor prognosis in glioma 21. In the present study, we found miR-362 to be downregulated in CRC tissues and cell lines, and discovered that low expression of miR-362 predicted poor overall survival in CRC patients.…”

Section: Introductionsupporting

confidence: 58%

MicroRNA-362 Inhibits Cell Proliferation and Invasion by Directly Targeting SIX1 in Colorectal Cancer

Wan

Yang²,

Qiao

et al. 2019

Yonsei Med J

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Purpose Colorectal cancer (CRC) is the third most common cancer in China and poses high morbidity and mortality. In recent years, increasing evidence has indicated that microRNAs played important functions in the occurrence and development of tumors. The purpose of this study was to identify the biological mechanisms of miR-362 in CRC. Materials and Methods Quantitative real-time PCR was carried out to assess the expression of miR-362 and SIX1. The Kaplan-Meier method was employed to evaluate the 5-year overall survival of CRC patients. The proliferative and invasive abilities of CRC cells were assessed by MTT and transwell assays. Results miR-362 was significantly decreased in CRC tissues and cell lines, compared to the normal tissues and normal cells. A significant connection was confirmed between the overall survival of 53 CRC patients and low expression of miR-362. Downregulation of miR-362 inhibited the proliferation and invasion through binding to the 3′-UTR of SIX1 mRNA in CRC. Additionally, we discovered that SIX1 was a direct target gene of miR-362 and that the expression of miR-362 had a negative connection with SIX1 expression in CRC. SIX1 could reverse partial functions in the proliferation and invasion in CRC cells. Conclusion miR-362 may be a prognostic marker in CRC and suppress CRC cell proliferation and invasion in part through targeting the 3′-UTR of SIX1 mRNA. The newly identified miR-362/SIX1 axis provides insight into the progression of CRC.

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Section: Introductionsupporting

confidence: 58%

MicroRNA-362 Inhibits Cell Proliferation and Invasion by Directly Targeting SIX1 in Colorectal Cancer

Wan

Yang²,

Qiao

et al. 2019

Yonsei Med J

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“…Concerning ANGPT2 , the methylation status of 6 CpGs near the gene transcription site (four of which were analyzed in this study) has already been shown to predict overall survival of chronic lymphocytic leukemia patients (Martinelli et al ., ). Several studies have reported that SIX1 overexpression is frequently associated with poor patient prognosis in various malignancies, as colorectal cancer (Kahlert et al ., ) and glioma (Zhang and Xu, ), however not in melanoma. Besides, the mechanisms responsible for the high expression of SIX1 have been poorly investigated.…”

Section: Discussionmentioning

confidence: 98%

Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma

et al. 2019

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The high mortality rate of melanoma is broadly associated with its metastatic potential. Tumor cell dissemination is strictly dependent on vascularization; therefore, angiogenesis and lymphangiogenesis play an essential role in metastasis. Hence, a better understanding of the players of tumor vascularization and establishing them as new molecular biomarkers might help to overcome the poor prognosis of melanoma patients. Here, we further characterized a linear murine model of melanoma progression and showed that the aggressiveness of melanoma cells is closely associated with high expression of angiogenic factors, such as Vegfc , Angpt2, and Six1, and that blockade of the vascular endothelial growth factor pathway by the inhibitor axitinib abrogates their tumorigenic potential in vitro and in the in vivo chicken chorioallantoic membrane assay. Furthermore, analysis of The Cancer Genome Atlas data revealed that the expression of the angiogenic factor ANGPT2 ( P ‐value = 0.044) and the lymphangiogenic receptor VEGFR‐3 ( P ‐value = 0.002) were independent prognostic factors of overall survival in melanoma patients. Enhanced reduced representation bisulfite sequencing‐based methylome profiling revealed for the first time a link between abnormal VEGFC , ANGPT2, and SIX1 gene expression and promoter hypomethylation in melanoma cells. In patients, VEGFC ( P ‐value = 0.031), ANGPT2 ( P ‐value < 0.001), and SIX1 ( P ‐value = 0.009) promoter hypomethylation were independent prognostic factors of shorter overall survival. Hence, our data suggest that these angio‐ and lymphangiogenesis factors are potential biomarkers of melanoma prognosis. Moreover, these findings strongly support the applicability of our melanoma progression model to unravel new biomarkers for this aggressive human disease.

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“…[23][24][25] In our concurrent study, in cultured melanoma cells, SIX1 was proven to promote cell proliferation and invasion, and SIX1 expression could be inhibited by miR-150-5p, which exhibited inhibitory functions in melanoma cell. 26 However, the in vivo metastatic functions and the clinical significance of SIX1 in melanoma are unknown. Thus, underlying the mechanisms of SIX1 regulation in melanoma and the upstream factors of SIX1 would be conducive to clinical treatments.…”

Section: Discussionmentioning

confidence: 99%

miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential

Yang

Zhu²,

Zhang

et al. 2020

Molecular Therapy - Oncolytics

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Sine oculis homeobox 1 (SIX1), a key transcription factor for regulating aerobic glycolysis, participates in the occurrence of various cancer types. However, the role of SIX1 in melanoma and the upstream regulating mechanisms of SIX1 remain to be further investigated. MicroRNAs (miRNAs) have emerged as key regulators in tumorigenesis and progression. Here, we show that miR-489-3p suppresses SIX1 expression by directly targeting its 3 0 untranslated region (3 0 UTR) in melanoma cells. miR-489-3p suppressed melanoma cell proliferation, migration, and invasion through inhibition of SIX1. Mechanistically, by targeting SIX1, miR-489-3p dampens glycolysis, with decreased glucose uptake, lactate production, ATP generation, and extracellular acidification rate (ECAR), as well as an increased oxygen consumption rate (OCR). Importantly, glycolysis regulated by the miR-489-3p/SIX1 axis is critical for its regulation of melanoma growth and metastasis both in vitro and in vivo. In melanoma patients, miR-489-3p expression is negatively correlated with SIX1 expression. In addition, patients who had increased glucose uptake in tumors and with metastasis assessed by positron emission tomography (PET) scans showed decreased miR-489-3p expression and increased expression of SIX1. Collectively, our study demonstrates the importance of the miR-489-3p/SIX1 axis in melanoma, which can be a potential and a promising therapeutic target in melanoma.

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Six1 expression is associated with a poor prognosis in patients with glioma

Cited by 15 publications

References 42 publications

MicroRNA-362 Inhibits Cell Proliferation and Invasion by Directly Targeting SIX1 in Colorectal Cancer

MicroRNA-362 Inhibits Cell Proliferation and Invasion by Directly Targeting SIX1 in Colorectal Cancer

Gene expression and promoter methylation of angiogenic and lymphangiogenic factors as prognostic markers in melanoma

miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential

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