Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma

Chao, Lemeng; Liu, Jianfeng; Zhao, Dewei

doi:10.3892/ol.2017.5803

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…3 Additionally, increased SIX1 level is associated with poor survival outcome of osteosarcoma patients. 4 However, the biological function of SIX1 in HCC is rarely investigated.…”

Section: Introductionmentioning

confidence: 99%

SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53

Cheng

Deng

Jin

et al. 2018

Cancer Biology & Therapy

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S This research aimed to explore effects of SIX1 and DACH1 on hepatocellular carcinoma (HCC) cell proliferation, apoptosis and cell cycle. Fifty paired hepatocellular carcinoma tissues were screened for differentially expressed genes. SIX1 and DACH1 expressions were subjected to qRT-PCR and western blot in tumor tissues and cells. The knockdown efficiency of siRNAs and transfection efficiency of cDNAs and siRNAs were validated by qRT-PCR and western blot as well. Then colony formation assay and flow cytometry were applied to observe cell proliferation, cell apoptosis and cell cycle changes. Immunofluorescence co-localization and immunoprecipitation were used to analyze the interaction between proteins which was quantified using western blot. Effects of SIX1 and DACH1 on tumor growth and their expressions in tumors were confirmed in vitro in nude mice model. Results of these experiments showed that SIX1 was overexpressed while DACH1 was suppressed in HCC tissues and cells. The suppression of SIX1 and overexpression of DACH1 not only inhibited cell proliferation, but also induced cell apoptosis and arrested cell cycle in G2/M phase compared with control group. Results of immunofluorescence co-localization suggested that SIX1, p53 and DACH1 were significantly overlapped. Immunoprecipitation showed that DACH1 (marked with Flag tag) could pull down p53 and SIX1, but SIX1 (marked with His tag) could only pull down DACH1, which indicated that an indirect regulation between SIX1 and p53. Validated with western blot afterwards, DACH1 overexpression suppressed tumorigenesis in vivo by up-regulating p53 expression while SIX1 overexpression accelerated tumor growth by down-regulating p53 expression. Therefore, the decrease of SIX1 facilitated the expression of DACH1, thus activated the expression of p53 and suppressed the progression of HCC both in vitro and in vivo.

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“…3 Additionally, increased SIX1 level is associated with poor survival outcome of osteosarcoma patients. 4 However, the biological function of SIX1 in HCC is rarely investigated.…”

Section: Introductionmentioning

confidence: 99%

SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53

Cheng

Deng

Jin

et al. 2018

Cancer Biology & Therapy

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“…22 Moreover, multiple studies have demonstrated that high SIX1 expression leads to poor survival in a variety of cancers. [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.…”

Section: Discussionmentioning

confidence: 76%

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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“…Previous studies have shown that SIX1 expression is correlated with the prognosis of multiple types of cancer (26,27). Therefore, the present study investigated SIX1 expression in NSCLC tissues.…”

Section: Six1 Expression Is Upregulated In Nsclc Tissues and Correlat...mentioning

confidence: 99%

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Chen²,

Qin³

et al. 2022

Oncol Lett

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Aerobic glycolysis plays a key role in cancer cell metabolism and contributes to tumorigenesis, including that of non-small cell lung cancer (NSCLC). Tanshinone IIA (Tan IIA), an active compound of Salvia miltiorrhiza, exhibits antitumor properties. Multiple mechanisms are involved in the antitumor action of Tan IIA in lung cancer, such as inhibiting cell growth, promoting cell apoptosis and influencing cellular metabolism. However, the effects of Tan IIA on NSCLC cells and its mechanisms of action remain unclear. The present study shows Tan IIA dose-dependently attenuated the growth of NSCLC cells and in vitro in a dose-dependent manner. Moreover, Tan IIA markedly decreased the ATP level, glucose uptake and lactate production in the NSCLC cells in vitro. Tan IIA also inhibited tumor growth in a xenograft model in vivo. Mechanically, Tan IIA treatment decreased sine oculis homeobox homolog 1 (SIX1) mRNA and protein levels, thus leading to the downregulation of pyruvate kinase isozyme M2, hexokinase 2 and lactate dehydrogenase A (LDHA) expression in A549 cells. SIX1 knockdown with small interfering-RNA inhibited glycolysis in NSCLC cells, suggesting that SIX1 plays a role in the antitumor effect of Tan IIA on NSCLC cells. More importantly, it was demonstrated that SIX1 expression was stimulated in patients with NSCLC and was positively correlated with the LDH serum level. Finally, SIX1 low expression levels predicted the poor prognosis of patients with NSCLC. In conclusion, the present study showed that Tan IIA functioned as an anti-glycolysis agent in NSCLC cells by downregulating SIX1 expression and inhibiting cell proliferation.

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Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma

Cited by 14 publications

References 37 publications

SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53

SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53

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

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

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