HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer

Song, Chenlong; Han, Yang; Luo, Huan; Qin, Zhiwei; Chen, Zhengqian; Liu, Yuan; Lu, Su; Sun, Huimin; Zhou, Chongzhi

doi:10.1002/cam4.2440

Cited by 42 publications

(33 citation statements)

References 35 publications

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“…Decreased expression of HOXA10 accelerated the acetylation of p53 (Lys382) and suppressed the transcription of histone deacetylase 1 (HDAC1; a potential deacetylase for p53) to activate p53 transcription (26). Additionally, HOXA10 might promote cell proliferation by elevating Bcl-2 expression and inhibiting apoptosis in gastric cancer, and high expression of HOXA10 predicted poor overall survival in gastric cancer patients (27). In this study, we found high expression of HOXA10 in LSCC tissues.…”

Section: Discussionmentioning

confidence: 64%

Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer

Zhou

2020

Front. Oncol.

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The homeobox A cluster (HOXA) gene family, comprising 11 members, is involved in a wide spectrum of biological functions in human cancers. However, there is little research on the expression profile and prognostic values of HOXA genes in laryngeal squamous cell cancer (LSCC). Based on updated public resources and integrative bioinformatics analysis, we assessed the expression profile and prognostic values of the HOXA family members. Expression and methylation data on HOXA family members were obtained from The Cancer Genome Atlas (TCGA). The prognostic values of HOXA members and clinical features were identified. A gene set enrichment analysis (GSEA) was conducted to explore the mechanism underlying the involvement of HOXA members in LSCC. The associations between tumor immune infiltrating cells (TIICs) and the HOXA family members were evaluated using the Tumor Immune Estimation Resource (TIMER) database. HOXA2 and HOXA4 were downregulated and HOXA7 and HOXA9-13 were upregulated in LSCC. Upregulation of HOXA10, HOXA11, and HOXA13, along with two clinical characteristics (M stage and gender), were associated with a poor LSCC prognosis based on the results of univariate and multivariate Cox proportional hazards regression analyses. Although there were no significant correlations between TIICs and HOXA members, the GSEA results indicated that HOXA members participate in multiple biological processes underlying tumorigenesis. This study comprehensively analyzed the HOXA members, providing insights for further investigation of the HOXA family members as potential targets in LSCC.

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Section: Discussionmentioning

confidence: 64%

Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer

Zhou

2020

Front. Oncol.

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“…We have also identified previous research that supports their importance in cancer. High expression of HOXA10 can promote tumor development in gastric cancer, hepatocellular carcinoma, and ovarian cancer [19][20][21]. More importantly, downregulated LINC00483 suppresses tumor cell invasion, migration, and epithelial to mesenchymal transition.…”

Section: Discussionmentioning

confidence: 99%

A signature related to lung adenocarcinoma prognosis: A study based on TCGA database

Wang¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background: The intrinsic molecular subtypes of lung adenocarcinoma (LUAD) impact clinical treatment decision-making, but the molecular mechanisms are still unclear. Therefore, we aimed to identify sensitive biomarkers to evaluate LUAD patient prognosis. Methods: Differentially expressed RNAs from LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database and they were used to construct a competitive endogenous RNA (ceRNA) network. Based on the examination of clinical data, long noncoding RNAs (lncRNAs) and mRNAs in the network were selected by univariate and multivariate Cox regression analysis. Finally, functional enrichment analysis was used to reveal prognostic signatures based on the classification into high and low-risk groups, survival analysis, and an independence test. Results: The ceRNA network consisted of 21 mRNAs, 53 lncRNAs, and 8 miRNAs that were selected from the differentially expressed RNAs identified. Next, based on univariate and multivariate Cox regression analysis, a prognostic signature, including two mRNAs (HOXA10 and CBX2) and four lncRNAs (LINC00460, LINC00330, DGCR5, and C14orf132) was constructed. Eventually, survival analysis showed that significant differences in survival rates between high and low-risk groups and the area under the curve (AUC) for three‐year survival was 0.714. Compared with clinical risk factors, including age, pathological stage, and TNM stage, our risk score had a higher prognostic value. Conclusion: By screening from a ceRNA network, we constructed a signature, including two mRNAs (HOXA10 and CBX2) and four lncRNAs (LINC00460, LINC00330, DGCR5, and C14orf132), that can be utilized as a prognostic biomarker in LUAD. This signature may provide options for clinical treatment.

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“…OCT-4 is a homeobox gene well known for its function in generating induced pluripotent stem cells (Bhartiya, 2013;Seiler et al, 2011); this gene has also been identified as an oncogene known for promoting the features of cancer stem cells (Li et al, 2017;Phiboonchaiyanan & Chanvorachote, 2017). In addition to OCT-4, an increasing body of evidence reveals that homeobox genes may participate in the promotion of various malignant phenotypes such as the proliferation, migration and invasion of cancers (Hirao et al, 2019;Miwa & Kanda, 2019;Rodini et al, 2012;Song et al, 2019). We have previously reported that HoxC6, another member of homeobox superfamily, functions as an oncogene in ESCC (Tang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes

Cao

Wang

Tang

et al. 2020

PeerJ

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Background A number of homeobox genes have been implicated in the development of various cancers. However, the role of engrailed 2 (EN2), a member of the homeobox gene superfamily, in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods The expression of EN2 was examined using quantitative real-time PCR and immunohistochemistry. A stable cell line was established to express exogenous EN2 using a lentivirus system. The malignant phenotype was analyzed with proliferation, clonogenicity, wound-healing and invasion assays. The CRISPR/Cas9 system was adopted to deplete endogenous EN2. RNA profiling was performed using gene expression microarray. The ShRNA-mediated method was used to knock down the expression of SPARC. The structure-function relationship was determined using site-directed mutagenesis. Results EN2 is highly expressed in ESCC. The malignant phenotype of the ESCC cell line was amplified by an overexpression of EN2 but was attenuated by a disruption of EN2. RNA profiling analysis revealed that distinct sets of genes were modulated by the expression of EN2 in various ESCC cell lines and oncogenes were among these. EN2 greatly increased the expression of SPARC in Eca109. Site-directed mutagenesis revealed that the induction of SPARC was closely correlated with the protumor function of EN2. ShRNA-mediated knockdown of SPARC attenuated the malignant phenotype of EN2-infected cells. These data suggest that SPARC is crucial for mediating the protumor function of EN2. Discussion EN2 has an oncogenic function in ESCC that is mediated by upregulating the expression of pro-oncogenic genes downstream. EN2 may potentially act as a diagnostic marker or therapeutic target for ESCC treatment in the future.

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HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer

Cited by 42 publications

References 35 publications

Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer

Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer

A signature related to lung adenocarcinoma prognosis: A study based on TCGA database

Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes

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