Epigenetic Changes and Functional Study of
            <i>HOXA11</i>
            in Human Gastric Cancer

Cui, Yingying; Gao, Dan; Linghu, Enqiang; Zhan, Qimin; Chen, Runsheng; Brock, Malcolm V.; Herman, James G.; Guo, Mingzhou

doi:10.2217/epi.14.92

Cited by 40 publications

(37 citation statements)

References 46 publications

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“…In order to investigate the function of HOXA11 in breast cancer, we employed cell proliferation assay and observed an inhibition effect in all analyzed cell lines (Figure 3A). The similar response has been discovered in non-small cell lung cancer [8] and gastric cancer [22]. Based on previous studies and our results, HOXA11 is a potential tumor suppressor in breast cancer.…”

Section: Discussionsupporting

confidence: 89%

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Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

et al. 2016

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Homeobox A11 (HOXA11) is one of the hypermethylated genes in breast cancer and its function in breast tumorigenesis remains elusive. In this study, we analyzed the methylation status of HOXA11 in 264 paired breast cancer and normal tissue as well as in matched serum samples by MethyLight assay. Further, the function of HOXA11 in breast tumorigenesis was analyzed by cell proliferation and migration assays. We found that HOXA11 was hypermethylated in cancer tissues (45.08%), especially in invasive ductal carcinomas (P<0.001), patients with a family history of cancer (P=0.033), cases with metastatic lymph nodes (P=0.004) and P53 positive group (P=0.017). Kaplan-Meier survival analysis and Cox regression analysis revealed that HOXA11 hypermethylation is an independent predictor of poor outcomes. The over expression of HOXA11 suppressed cell growth in MDA-MB-231, MCF7, SKBR3 and BT474 cells. In conclusion, the hypermethylation of HOXA11 is an independent prognostic biomarker in breast cancer. Additionally, HOXA11 can be a potential tumor suppressor.

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Section: Discussionsupporting

confidence: 89%

“…In addition, this phenomenon was also described in other malignancies [8, 22]. Hence, DNA methylation alone is sufficient to silence HOXA11 in tumors.…”

Section: Discussionmentioning

confidence: 63%

Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

et al. 2016

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“…The role HOXA11 in diverse cancers has been reported [41-47]. In gastric cancer, the epigenetic down-regulation of HOXA11 has been related to carcinogenesis, proliferation, migration, and invasion [41,42]. Similarly, in lung and ovarian cancers, the down-regulation of HOXA11 was shown to be a poor prognostic factor [43,44].…”

Section: Discussionmentioning

confidence: 99%

Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma

Bem

Kim

et al. 2017

Cancer Res Treat

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PurposeHomeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.Materials and MethodsThe full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.ResultsThe underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.ConclusionThe treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

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“…Hypermethylation and low expression of HOXA11 was reported in different cancers, such as ovarian cancer and endometrial cancer, and it functions as a tumor suppressor [13, 21]. In breast cancer, HOXA11 has been proposed as a biomarker that could be used for early detection [22]. In ovarian cancer, the methylation of HOXA11 has been reported to be a poor prognostic marker [13].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic inactivation ofHOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with RCC TNM classification

et al. 2017

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Epigenetic inactivation of HOXA11, a putative tumor suppressor, is frequently observed in a number of solid tumors, but has not been described in RCC (renal cell carcinoma). In this study, we investigated the expression, epigenetic changes and the function of HOXA11 in human renal cell carcinoma (RCC). HOXA11 was silenced or down-regulated in RCC cell lines and tissues. Methylation specific PCR (MSP) and bisulfite genomic sequencing (BGS) revealed that the HOXA11 promoter was hypermethylated in 5/6 RCC cell lines. Demethylation treatment resulted in demethylation of the promoter and increased HOXA11 expression in these cell lines. HOXA11 methylation was also detected in 68/95 (70.5%) primary RCC tumors, but only rare adjacent non-malignant renal tissues (13%, 3/23) showed hypermethylation of promoter. We also found that the methylation of HOXA11 was associated with higher TNM classification of RCC (p<0.05). Ectopic expression of HOXA11 led to significant inhibition of proliferation, colony formation, migration and invasion abilities and induced RCC cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Thus, our study demonstrated that HOXA11 function as a tumor suppressor in RCC, while it is frequently silenced by promoter methylation in RCC.

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Epigenetic Changes and Functional Study of HOXA11 in Human Gastric Cancer

Abstract: Epigenetic silencing of HOXA11 promotes GC proliferation, migration and invasion through activation of Wnt signaling.

Cited by 40 publications

References 46 publications

Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma

Epigenetic inactivation ofHOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with RCC TNM classification

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