HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Li, Na; Gou, Jinhai; Xiong, Jianping; You, Juan-juan; Li, Zhengyu

doi:10.1186/s12885-020-06725-4

Cited by 10 publications

(9 citation statements)

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“…HOXB4, a member of the Antp homeobox protein family, regulates embryonic development and participates in tumor progression as an oncogene or tumor suppressor gene. In ovarian cancer, the expression of HOXB4 was closely related to poor prognosis and transcriptionally activated DHDDS to stimulate the proliferation and invasion of tumor cells 23 . Other studies also revealed that HOXB4 was upregulated in ovarian cancer cells and drug-resistant cells 35 .…”

Section: Discussionmentioning

confidence: 99%

“…HOXB4, the positive regulator implicated in the self-renewal of hematopoietic stem cells (HSCs) 21 , has been recognized as an oncogene or a tumor suppressor gene, depending on the specific type of cancer. HOXB4 was overexpressed in many cancers, including ovarian cancer 22 , 23 , cervical cancer 24 – 27 , lung cancer 28 , renal cancer 29 , mesothelioma 30 , and leukemia 31 – 34 , which promoted tumor growth and metastasis 23 . Moreover, increased HOXB4 expression resulted in drug resistance 31 , 35 .…”

Section: Introductionmentioning

confidence: 99%

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HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

2021

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Homeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

2021

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“…CORO6 is a member of the coronin family and is an actin-binding protein [ 27 , 28 ]. HOXB4 is associated with the prognosis of ovarian cancer patients, leukemia resistance, and renal cancer [ 29 – 31 ]. RNF212 is associated with postoperative survival rate and TMZ chemoradiation response in GBM patients as well as mammalian meiosis [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

et al. 2021

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Ubiquitination is a dynamic and reversible process of a specific modification of target proteins catalyzed by a series of ubiquitination enzymes. Because of the extensive range of substrates, ubiquitination plays a crucial role in the localization, metabolism, regulation, and degradation of proteins. Although the treatment of glioma has been improved, the survival rate of patients is still not satisfactory. Therefore, we explore the role of ubiquitin proteasome in glioma. Survival-related ubiquitination related genes (URGs) were obtained through analysis of the Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA). Cox analysis was performed to construct risk model. The accuracy of risk model is verified by survival, Receiver operating characteristic (ROC) and Cox analysis. We obtained 36 differentially expressed URGs and found that 25 URGs were related to patient prognosis. We used the 25 URGs to construct a model containing 8 URGs to predict glioma patient risk by Cox analysis. ROC showed that the accuracy rate of this model is 85.3%. Cox analysis found that this model can be used as an independent prognostic factor. We also found that this model is related to molecular typing markers. Patients in the high-risk group were enriched in multiple tumor-related signaling pathways. In addition, we predicted TFs that may regulate the risk model URGs and found that the risk model is related to B cells, CD4 T cells, and neutrophils.

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“…It has been reported that HOXB4 participates in the advancement of ovarian cancer, as well as lung, prostate, and breast cancer ( 13 ). A previous report has shown that elevated HOXB4 expression facilitates the ovarian cancer progression via DHDDS ( 14 ). However, HOXB4 attenuates the tumorigenesis of cervical cancer cells by declining the Wnt/β-catenin signaling pathway activity ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

HOXB4 Mis-Regulation Induced by Microcystin-LR and Correlated With Immune Infiltration Is Unfavorable to Colorectal Cancer Prognosis

et al. 2022

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Microcystin-LR (MC-LR) exists widely in polluted food and water in humid and warm areas, and facilitates the progression of colorectal cancer (CRC). However, the molecular mechanism associated with the MC-LR-induced CRC progression remains elusive. The purpose of this study is to explore the role of the hub genes associated with MC-LR-induced CRC development at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. By utilizing R, we screened and investigated the differentially expressed genes (DEGs) between the MC-LR and the control groups with the GEO, in which, HOXB4 highly expressed in MC-LR-treated group was identified and further explored as a hub gene. With the aid of TCGA, GEPIA, HPA, UALCAN, Cistrome, and TIMER, the increased mRNA and protein levels of HOXB4 in CRC tissue were found to be positively associated with high tumor stage and poor prognosis, and were linked to immune infiltration, especially tumor-associated macrophages and cancer-associated fibroblasts. Cox regression analysis and nomogram prediction model indicated that high HOXB4 expression was correlated to poor survival probability. To elucidate the mechanism of high HOXB4 expression induced by MC-LR, we overlapped the genes involved in the MC-LR-mediated CRC pathways and the HOXB4-correlated transcription genes. Importantly, C-myc instead of PPARG and RUNX1 promoted the high expression of HOXB4 through experiment validation, and was identified as a key target gene. Interestingly, C-myc was up-regulated by HOXB4 and maintained cell cycle progression. In addition, MC-LR was proved to up-regulate HOXB4 expression, thus promoting proliferation and migration of Caco2 cells and driving the cell cycle progression. In conclusion, MC-LR might accelerate CRC progression. In the process, MC-LR induced C-myc augmentation elevates the high expression of HOXB4 through increasing the S phase cell proportion to enhance Caco2 cell proliferation. Therefore, HOXB4 might be considered as a potential prognostic biomarker for CRC.

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HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Cited by 10 publications

References 50 publications

HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

HOXB4 Mis-Regulation Induced by Microcystin-LR and Correlated With Immune Infiltration Is Unfavorable to Colorectal Cancer Prognosis

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