Upregulation of <scp>SIX4</scp> indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma

Li, Yanping; Jiang, Xiaomei; Yan, Xiaoyan; Wang, Yanzheng

doi:10.1111/1759-7714.13832

Cited by 8 publications

(8 citation statements)

References 21 publications

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“… 17 , 18 SIX4 belongs to the sine oculis homeobox family that has been reported to be required for tumour progression, such as leukaemia, oesophageal squamous cell carcinoma, hepatocellular carcinoma and pancreatic ductal adenocarcinoma. 8 , 9 , 19 , 20 …”

Section: Discussionmentioning

confidence: 99%

“…The sine oculis homeobox 4 (SIX4) transcription factor, which belongs to the superfamily of homeobox gene family, has been identified contributes to tumour initiation, progression and metastasis 7 . For example, upregulation of SIX4 promotes tumour growth or metastasis in oesophageal squamous cell carcinoma, hepatocellular carcinoma and breast cancer 8–10 . These findings indicate that deregulation of SIX4 plays critical roles in cancer progression and metastasis.…”

Section: Introductionmentioning

confidence: 99%

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SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression

Dang

Duan

et al. 2023

J Cellular Molecular Medi

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Metabolism reprogramming plays an important role in tumorigenesis and osteosarcoma metastasis. Sine oculis homeobox 4 (SIX4) is reported to be a key transcription factor that is involved in glycolysis reprogramming of cancer cells. However, the role of SIX4 in osteosarcoma progression remains unknown. The expression profile of SIX4 in OS was evaluated in surgery samples of osteosarcoma patients. Functional studies were performed in vitro and in vivo. We found that SIX4 is significantly overexpressed in osteosarcoma and related to the undesirable prognosis of osteosarcoma patients. SIX4 promotes progression of osteosarcoma via upregulating isocitrate dehydrogenase 1 (IDH1), which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression

Dang

Duan

et al. 2023

J Cellular Molecular Medi

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“…SIX4 fulfills an important role in the development of multiple tumors. A previous study indicated that the upregulation of SIX4 is an indicator of poor clinical prognosis of esophageal squamous cell carcinoma, and that this leads to the promotion of tumor growth and cell metastasis ( 8 ). SIX4 is able to promote hepatocellular carcinoma metastasis via upregulation of the proteins Yes associated transcriptional regulator 1 and C-Met ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…SIX homeobox 4 (SIX4), a member of the homeobox family, subfamily SIX, was first found to regulate the expression of Na + /K + -ATPase subunit ( 7 ). Previous studies have demonstrated that the gene expression levels of SIX4 are closely associated with the occurrence, development, invasion, metastasis and prognosis of esophageal squamous cell carcinoma ( 8 ), breast cancer ( 9 ), bladder cancer ( 10 ), non-small cell lung cancer ( 11 ) and other tumor types, suggesting that the SIX4 gene may function as an oncogene in the development of a wide variety of tumors. In addition, a previous study has revealed that SIX4 is involved in the differentiation of epithelial follicular stem cells in the ovaries of Drosophila ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

IGF2BP3‑stabilized SIX4 promotes the proliferation, migration, invasion and tube formation of ovarian cancer cells

Han

2022

Mol Med Rep

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The mortality rate of ovarian cancer (OC) is the highest among the different types of female reproductive system cancers. SIX homeobox 4 (SIX4), a member of the homeobox family, subfamily SIX, fulfills an important role in metastasis and angiogenesis in a variety of types of cancer. The aim of the present study was to investigate both the effects and the underlying mechanism of SIX4 on angiogenesis in OC. The Gene Expression Profiling Interactive Analysis and Encyclopedia of RNA Interactomes databases were employed to predict the expression levels of SIX4 in OC tissues, and its association with the overall survival (OS) rate of patients with OC. The expression levels of SIX4 in OC cell lines were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Following silencing of SIX4, the proliferation, invasion, migration and angiogenesis of OC cells were investigated via Cell Counting Kit-8, colony formation, wound healing, Transwell and tube formation assays. Subsequently, the levels of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in OC cell lines were detected by RT-qPCR and western blot analysis. The ability of IGF2BP3 to bind to SIX4 mRNA was detected via an RNA immunoprecipitation assay, and the stability of SIX4 mRNA was assessed by RT-qPCR following Actinomycin D treatment. Finally, the effects of transfection of sh-SIX4 and overexpression of IGF2BP3 simultaneously were examined to further delineate the mechanism involved. It was revealed that SIX4 was highly expressed in OC tissues and cells, and its expression was associated with low OS rates in patients with OC. SIX4 knockdown with short hairpin RNA inhibited the proliferation, migration and invasion of cells, as well as angiogenesis. In addition, IGF2BP3 overexpression led to an improvement in the stability of SIX4 mRNA. Overexpression of IGF2BP3 also reversed the inhibitory effect of SIX4 interference on the malignant phenotypes of OC cells. Taken together, the results of the present study demonstrated that IGF2BP3-stabilized SIX4 promoted the proliferation, metastasis and angiogenesis of SKOV3 cells.

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“…In the present study, SIX4 was identified as a downstream target of FOXA1 using a bioinformatics tool hTFtarget ( http://bioinfo.life.hust.edu.cn/hTFtarget#!/ ). SIX4 has been lately revealed to indicate dismal clinical outcome of patients with esophageal squamous cell carcinoma and to potentiate tumor growth and cell metastasis [ 11 ]. However, its role in CC, especially in regulating chemoresistance, remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance

Wang

Sun

Chen

et al. 2022

Analytical Cellular Pathology

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Cervical cancer (CC) is among the most prevalent cancers among female populations with high recurrence rates all over the world. Cisplatin (DDP) is the first-line treatment for multiple cancers, including CC. The main problem associated with its clinical application is drug resistance. This study is aimed at investigating the function and downstream regulation mechanism of forkhead-box A1 (FOXA1) in CC, which was verified as an oncogene in several cancers. Using GEO database and bioinformatics analysis, we identified FOXA1 as a possible oncogene in CC. Silencing of FOXA1 inhibited CC cell growth, invasion, and chemoresistance. Afterwards, the downstream gene of FOXA1 was predicted using a bioinformatics website and validated using ChIP and dual-luciferase assays. SIX4, a possible target of FOXA1, promoted CC cell malignant aggressiveness and chemoresistance. In addition, overexpression of SIX4 promoted phosphorylation of PI3K and AKT proteins and activated the PI3K/AKT signaling pathway. Further overexpression of SIX4 reversed the repressive effects of FOXA1 knockdown on CC cell growth, invasion, and chemoresistance in DDP-resistant cells. FOXA1-induced SIX4 facilitates CC progression and chemoresistance, highlighting a strong potential for FOXA1 to serve as a promising therapeutic target in CC.

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Upregulation of SIX4 indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma

Cited by 8 publications

References 21 publications

SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression

SIX4 upregulates IDH1 and metabolic reprogramming to promote osteosarcoma progression

IGF2BP3‑stabilized SIX4 promotes the proliferation, migration, invasion and tube formation of ovarian cancer cells

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance

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