The Widening Sphere of Influence of HOXB7 in Solid Tumors

Errico, Maria Cristina; Jin, Kideok; Sukumar, Saraswati; Caré, Alessandra

doi:10.1158/0008-5472.can-15-3444

Cited by 31 publications

(30 citation statements)

References 39 publications

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“…HOXB7 is commonly believed to be dysregulated in several types of cancers and associated with cancer progression [24]. HOXB7 upregulation has been demonstrated in colorectal cancer and esophageal squamous cell carcinoma, and HOXB7 has been shown to indicate poor prognosis in individuals with both these diseases [20, 21].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, its expression has been correlated with clinical progression and poor outcome and may serve as a potential prognostic factor and therapeutic target [11, 14, 19, 20, 22, 23]. HOXB7 is involved in many of the major cellular processes that occur in cancer, including proliferation, invasion, migration, angiogenesis and the epithelial–mesenchymal transition (EMT) [24]. Furthermore, HOXB7 has been reported to facilitate the migration of breast [25] and liver [18] cancer cells by inducing EMT, and ectopic expression of HOXB7 promotes angiogenesis [9, 26] and cell proliferation [17, 18].…”

Section: Introductionmentioning

confidence: 99%

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Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

Dai

Yang

et al. 2019

Laboratory Investigation

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Homeobox B7 (HOXB7) protein is reported to be aberrantly expressed in a variety of cancers and to play an important role in multiple cellular processes. However, the specific mechanism by which HOXB7 promotes the malignant progression of intrahepatic cholangiocarcinoma (ICC) remains unclear. Therefore, we used quantitative real-time polymerase chain reaction (PCR) to detect the expression level of HOXB7 in 38 paired ICC tissue samples. Additionally, to assess correlation between HOXB7 and ICC prognosis, we performed immunohistochemistry (IHC) using 122 ICC tissues to detect HOXB7 expression. Cell Counting Kit-8 (CCK-8) and colony formation assays were employed to assess ICC cell proliferation, and Transwell assays were performed to estimate the invasion and migration abilities of ICC cells. The capillary tube formation assay was applied to explore the angiogenic effects of HOXB7. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth and lung metastasis. The results showed higher expression of HOXB7 in ICC tissues than in noncancerous tissues, and this increased expression was significantly associated with a poor prognosis. In addition, HOXB7 overexpression enhanced capillary tube formation, invasion and migration of ICC cells in vitro, whereas HOXB7 knockdown produced the opposite results in vitro. Moreover, the role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that the expression levels of MMP2, MMP9, VEGFa, and IL8 were elevated by HOXB7 and that the ERK pathway was activated. Our results demonstrate the prognostic value of HOXB7 and its role in metastasis and angiogenesis in ICC. HOXB7 upregulated MMP2, MMP9, VEGFa, and IL8 expression via the ERK pathway to accelerate the malignant progression of ICC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

Dai

Yang

et al. 2019

Laboratory Investigation

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“…It is generally recognized that HOXB7 is dysregulated in several types of cancers and associated with cancer progression [ 10 ]. HOXB7 up-regulation has been demonstrated in gastric cancer and shown to indicate poor prognosis in gastric cancer patients [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Homeobox B7 (HOXB7), a member of homeobox gene family, has been shown to be involved in several cancers, including gastric [ 6 ], oral [ 7 ], pancreatic [ 8 ] and breast cancer [ 9 ]. As an important transcription factor, HOXB7 regulates many cancer cell functions, including proliferation, invasion, migration, angiogenesis and epithelial-mesenchymal transition (EMT) [ 10 ]. It has been reported that the proliferation and self-renewal of haematopietic stem cells are enhanced by HOXB7 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

Huan

Yang

Wen

et al. 2017

J Exp Clin Cancer Res

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BackgroundHomeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined.MethodsImmunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and wound-healing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo.ResultsHigher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated.ConclusionOverexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC.

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“…One functional study highlighted MAGI2-AS3 as a bladder cancer suppressor (Wang et al, 2018), while the other study focused on its effects on breast cancer cell growth (Yang et al, 2018). A member of HOX family, HOXB7 has also been highlighted to participate in a variety of crucial cellular processes during oncogenesis (Errico et al, 2016), with particular involvement in gastric cancer, wherein its over-expression promoted cell migration and invasion while restraining cell apoptosis (Joo et al, 2016). More importantly, over-expression of HOXB7 imparts reduced sensitivity of oral cancer cells to chemo-radiotherapy (Yuan et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2

Cheng

Shi

Lin

et al. 2020

Front. Cell Dev. Biol.

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BackgroundAccumulating evidence has suggested that aberrant expression of long non-coding RNAs (lncRNAs) may contribute to cancer progression in association with radioresistance. The current study aimed to identify the potential role of lncRNA MAGI2-AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells.Methods and ResultsInitially, we detected high expression of HOXB7 from microarray-based gene expression profiling of esophageal cancer. Then, we identified the interactions among MAGI2-AS3, HOXB7, and EZH2 by dual-luciferase reporter gene assay, RNA pull-down assay, RIP assay and ChIP assay. HOXB7 was highly-expressed, while MAGI2-AS3 was poorly-expressed in esophageal cancer tissues and cells. The effect of MAGI2-AS3 and HOXB7 on esophageal cancer cell proliferation and apoptosis as well as tumorigenicity of radioresistant cells was examined by gain- and loss-of-function experiments. Interestingly, MAGI2-AS3 down-regulated HOXB7 through interaction with EZH2, which promoted cell apoptosis and inhibited proliferation and radio-resistance. Besides, down-regulation of MAGI2-AS3 exerted a promoting effect on these malignant phenotypes.ConclusionTaken together, our results reveal the potential role of MAGI2-AS3 over-expression in controlling esophageal cancer resistance to radiotherapy by down-regulating HOXB7, this providing a candidate biomarker for resistance to radiotherapy.

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The Widening Sphere of Influence of HOXB7 in Solid Tumors

Cited by 31 publications

References 39 publications

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2

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