Overexpression of <i>HOXC10</i> promotes glioblastoma cell progression to a poor prognosis via the PI3K/AKT signalling pathway

Guan, Yanhua; He, Yajie; Lv, Shaoping; Hou, Xiaoqun; Luo, Li; Song, Jianjun

doi:10.1080/1061186x.2018.1473408

Cited by 24 publications

(30 citation statements)

References 24 publications

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“…HOXC10 has been reported to be oncogenic in other tumors (12,13), but in the present study, the results indicated that HOXC10 served as an antioncogene. This discrepancy regarding the function of HOXC10 in liver cancer and other tumors may be associated with the heterogeneity of tumors, such as metastasis associated lung adenocarcinoma transcript 1 in breast cancer (27) and p53 in hepatoma carcinoma (28).…”

Section: Discussioncontrasting

confidence: 66%

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Zhao

Guo

et al. 2020

Oncol Lett

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Homeodomain-containing gene 10 (HOXC10) is associated with the progression of a variety of different types of human cancer; however, the role of HOXC10 in liver cancer is not completely understood. The present study aimed to investigate the mechanisms underlying the effects of HOXC10 on liver cancer tumorigenesis. Quantitative PCR and western blotting were used to detect the expression patterns of HOXC10 in cancer and adjacent healthy tissues. EdU, Cell Counting Kit-8 and colony formation assays were used to determine the functions of HOXC10 in liver cancer cell lines. ENCORI, TargetScan and miRTarBase were used to identify microRNAs that target HOXC10. The verification of the interaction between HOXC10 and microRNA-221 was determined by a luciferase assay. Compared with adjacent non-cancerous tissues, the expression of HOXC10 was markedly decreased in liver cancer tissues. A HOXC10 small interfering (si)RNA significantly attenuated HOXC10 expression at the mRNA and protein levels, and enhanced cell proliferation compared with the siRNA-negative control group. In addition, the luciferase reporter assay indicated that microRNA-221 directly bound to the 3'-untranslated region of HOXC10, and interfered with the inhibitory effect of HOXC10 on proliferation. In addition, HOXC10 knockdown elevated the expression levels of mitogen-activated protein kinase signaling pathway markers compared with the siRNA-negative control group. Therefore, the results of the present study may aid with the development of novel therapeutic regimens and diagnostic markers of liver cancer.

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Section: Discussioncontrasting

confidence: 66%

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Zhao

Guo

et al. 2020

Oncol Lett

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“…It was shown that the survival time of patients with high HOXB7 or HOXC6 or HOXC8 expression was significantly shorter than that of patients with low expression, which is similar to the results of other groups . As reported, the consequences of dysregulated HOX genes in carcinogenesis can be interpreted as an extension of their normal function . Given that HOX genes can be viewed as global regulators of growth and differentiation, we investigated whether they could modulate the malignant phenotype in esophageal cancer.…”

Section: Discussionsupporting

confidence: 83%

“…[27][28][29] As reported, the consequences of dysregulated HOX genes in carcinogenesis can be interpreted as an extension of their normal function. [30][31][32] Given that HOX genes can be viewed as global regulators of growth and differentiation, we investigated whether they could modulate the malignant phenotype in es- Consequently, it becomes difficult to interpret these data and determine the exact contribution of any of these individual genes to a malignant phenotype. In addition, the general difficulty in developing effective small molecule inhibitors against transcription factors have proven significant barriers to consider individual HOX genes as therapy targets.…”

Section: Discussionmentioning

confidence: 99%

Targeting HOX/PBX dimer formation as a potential therapeutic option in esophageal squamous cell carcinoma

Shen

Zhou

et al. 2019

Cancer Science

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Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis, which are a family of transcriptional factors involved in determining cell identity during early development, and also dysregulated in many malignancies. Previously, HOXB7 , HOXC6 and HOXC8 were found abnormally upregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with normal mucosa and seen as poor prognostic predictors for ESCC patients, and were shown to promote cell proliferation and anti‐apoptosis in ESCC cells. These three HOX members have a high level of functional redundancy, making it difficult to target a single HOX gene. The aim of the present study was to explore whether ESCC cells are sensitive to HXR9 disrupting the interaction between multiple HOX proteins and their cofactor PBX, which is required for HOX functions. ESCC cell lines (KYSE70, KYSE150, KYSE450) were treated with HXR9 or CXR9, and coimmunoprecipitation and immunofluorescent colocalization were carried out to observe HOX/PBX dimer formation. To further investigate whether HXR9 disrupts the HOX pro‐oncogenic function, CCK‐8 assay and colony formation assay were carried out. Apoptosis was assessed by flow cytometry, and tumor growth in vivo was investigated in a xenograft model. RNA‐seq was used to study the transcriptome of HXR9‐treated cells. Results showed that HXR9 blocked HOX/PBX interaction, leading to subsequent transcription alteration of their potential target genes, which are involved in JAK‐signal transducer and activator of transcription (STAT) activation and apoptosis inducement. Meanwhile, HXR9 showed an antitumor phenotype, such as inhibiting cell proliferation, inducing cell apoptosis and significantly retarding tumor growth. Therefore, it is suggested that targeting HOX/PBX may be a novel effective treatment for ESCC.

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“…However, HOXA11 expression was significantly downregulated in recurrent GBMs compared with primary GBMs [147]. Several other studies also reported the overexpression of specific HOX genes in GBM compared with non-neoplastic brain samples: HOXA1 [148], HOXA9 [150], HOXA13 [146], HOXB3 [151], HOXB7 [152], HOXB9 [153], HOXC6 [154], HOXC9 [155], HOXC10 [156,157], HOXD4 [158], and HOXD9 [126]. Among these genes, HOXA1, HOXA9, HOXA13, HOXB9, and HOXC10 were expressed in a grade-dependent manner [148,150,146,153,156].…”

Section: Aberrant Hox Gene Expression In Gliomamentioning

confidence: 88%

“…The genetic manipulation of HOXA5, A9, A10, A13, B3, B7, B9, C6, C9, C10, and D9 showed that their expression increases the viability of GBM cell lines [151,154,152,149,146,153,161,157,156,150,126,165,122], and five of them (HOXA9, A13, C6, C10, and D9) also reduce cell death [122,146,156,150,126,151]. HOXA7, A9, B7, B9, C9, and C10 also increased GBM cell lines migration capacity [166,152,153,157,156,150,165], while HOXA6, A13, B3, and B13 promoted increased invasion [166,152,153,157,167,156,150,151,165,146].…”

Section: Hox Genes Act Mostly As Oncogenes In Gliomamentioning

confidence: 99%

HOX gene cluster (de)regulation in brain: from neurodevelopment to malignant glial tumours

Gonçalves

Boiteux

Arnaud

et al. 2020

Cell. Mol. Life Sci.

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HOX genes encode a family of evolutionarily conserved homeodomain transcription factors that are crucial both during development and adult life. In humans, 39 HOX genes are arranged in four clusters (HOXA, B, C, and D) in chromosomes 7, 17, 12 and 2, respectively. During embryonic development, particular epigenetic states accompany their expression along the anterior-posterior body axis. This tightly regulated temporal-spatial expression pattern reflects their relative chromosomal localization, and is critical for normal embryonic brain development, when HOX genes are mainly expressed in the hindbrain and mostly absent in the forebrain region. Epigenetic marks, mostly polycombassociated, are dynamically regulated at HOX loci and regulatory regions to ensure the finely tuned HOX activation and repression, highlighting a crucial epigenetic plasticity necessary for homeostatic development. HOX genes are essentially absent in healthy adult brain, whereas they are detected in malignant brain tumours, namely gliomas, where HOX genes display critical roles by regulating several hallmarks of cancer. Here, we review the major mechanisms involved in HOX genes (de)regulation in the brain, from embryonic to adult stages, in physiological and oncologic conditions. We focus particularly on the emerging causes of HOX gene deregulation in glioma, as well as on their functional and clinical implications.

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Overexpression of HOXC10 promotes glioblastoma cell progression to a poor prognosis via the PI3K/AKT signalling pathway

Cited by 24 publications

References 24 publications

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Targeting HOX/PBX dimer formation as a potential therapeutic option in esophageal squamous cell carcinoma

HOX gene cluster (de)regulation in brain: from neurodevelopment to malignant glial tumours

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