The roles of HOXB7 in promoting migration, invasion, and anti‐apoptosis in gastric cancer

Joo, Moon Kyung; Park, Jong Jae; Yoo, Hyo Soon; Lee, Beom Jae; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young Tae

doi:10.1111/jgh.13330

Cited by 22 publications

(27 citation statements)

References 37 publications

(74 reference statements)

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“…As we were primarily interested in direct interaction partners, we performed an in silico target prediction analysis of potential complementary sequence seeds and a complementary literature search to further identify miR-196b-5p targets with a putative influence on cancer cell migration. The process in its entirety identified 2 candidate genes, HOXB7 and GALNT5 that have been previously implicated in gastric and cervical cancer cell migration and/or invasion (34,36,37). In colorectal cancer, a study by Liao and colleagues reported that HOXB7 is significantly correlated with invasive and aggressive characteristics and poor survival of patients.…”

Section: Discussionmentioning

confidence: 99%

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

Stiegelbauer

Vychytilova-Faltejskova

Karbiener

et al. 2017

Clinical Cancer Research

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miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation and The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments. Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts ( < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and and which in turn regulated colorectal cancer cell migration. The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. .

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Section: Discussionmentioning

confidence: 99%

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

Stiegelbauer

Vychytilova-Faltejskova

Karbiener

et al. 2017

Clinical Cancer Research

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“…To date, HOXC6 appears to promote colorectal cancer (CRC) cell proliferation and tumorigenesis [45]. Then, HOXB7 over-expression was observed in gastric cancer and ESCC [46,47]. Liu et al [16] reported that the abnormal expression of HOTAIR promotes NSCLC cell migration and metastasis, partially via the down-regulation of HOXA5.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data

Yang

Wen

et al. 2017

Horm Metab Res

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The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.

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“…Our results showed that the PI3K/AKT/c-Myc axis was modulated by HOXB7 to facilitate the acquisition of cancer stem-like properties in hepatoma cells. It has also been reported that gastric cancer cell metastasis is promoted by HOXB7 via the PI3K/AKT pathway [6, 32, 33]. The AKT pathway was involved in EMT and carcinogenesis via the up-regulation of Slug [34].…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant expression of homeobox genes is frequently detected in a variety of cancers [5]. 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].…”

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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The roles of HOXB7 in promoting migration, invasion, and anti‐apoptosis in gastric cancer

Abstract: Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects.

Cited by 22 publications

References 37 publications

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data

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

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