Abnormal expression of <i>HOXD11</i> promotes the malignant behavior of glioma cells and leads to poor prognosis of glioma patients

Wang, Jialin; Liu, Zhendong; Zhang, Cheng; Wang, Hongbo; Li, Ang; Lian, Xiaoyu; Ren, Zhishuai; Zhang, Wang; Wang, Yanbiao; Zhang, Bo; Pang, Bo; Gao, Yanzheng

doi:10.7717/peerj.10820

Cited by 10 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kristina et al reported that knockdown of the expression of HOXD11 repressed tumor growth and lung metastasis in Ewing's sarcoma [19]. In addition, the overexpression of HOXD11 was a poor prognostic biomarker in head and neck squamous cell carcinoma and gliomas by promoting tumor proliferation and invasion [17,20]. Our results rst revealed a signi cant association between HOXD11 expression and clinicopathological features as well as poor outcomes in a large PSCC cohort.…”

supporting

confidence: 59%

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

Tan

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Regional lymph node and distant metastasis are the most radical causes of high mortality in penile squamous cell carcinoma (PSCC) patients. However, the available biomarkers and detailed mechanisms underlying the metastasis of PSCC remain elusive. Here, we detected that HOXD11 was upregulated in tumors, especially in metastatic lymph nodes, highlighting its role in the progression of PSCC. We aimed to further explore the clinical significance, biofunctions and specific mechanisms of HOXD11. Methods Twelve PSCC tumors, metastatic lymph nodes and corresponding normal tissue pairs were examined by an RNA-seq panel of HOX genes to explore progressive biomarkers. The expression of HOXD11 was detected by qPCR and western blotting in our newly established PSCC cell lines. The clinical relevance and outcomes of HOXD11 were further validated in a large cohort of 267 PSCC patients by immunohistochemistry. Functional experiments in vitro and subcutaneous xenograft and footpad metastatic models were conducted to investigate the of HOXD11. The targeting relationship and mechanisms between HOXD11, miR-138-5p and FN1 were demonstrated by dual luciferase reporter assays and chromatin immunoprecipitation. Results HOXD11 expression was upregulated in PSCC tissues, especially in metastatic lymph nodes. High HOXD11 expression was associated with aggressive features, such as advanced pN stages, extranodal extension, pelvic lymph node and distant metastasis, and predicted poor survival. Furthermore, knockdown of HOXD11 not only inhibited cell proliferation, invasion and tumor growth but also reduced the burden of metastatic lymph nodes. Besides, miR-138-5p and FN1 reversed HOXD11-mediated oncogenic capacity. Mechanistic studies indicated that HOXD11 was post-transcriptionally regulated by miR-138-5p, bound to the promoter regions of FN1 activating the FN1/MMP2/MMP9 pathway to decompose the extracellular matrix and promoted epithelial mesenchymal transition-like phenotype metastasis. Conclusions HOXD11 promotes PSCC progression, predicting advanced disease with poor outcomes. HOXD11 could be a promising prognostic biomarker and potential therapeutic target for PSCC.

show abstract

supporting

confidence: 59%

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

Tan

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Multiple types of mutations and changes in expression in HOXD11 have been observed in lung cancer, Oral Squamous Cell Carcinoma, prostate cancer, ovarian cancer, and Head and Neck Squamous Cell Carcinoma. HOXD11 may also change cell growth, clonality, and metastatic potential in Ewing sarcoma [39].…”

Section: Evaluation Of High Score Selected Genes Based On Laplacian S...mentioning

confidence: 99%

“…Recent studies showed that HOXD11 is involved in various cancer-related signaling pathways such as cell cycle, DNA replication, ECM receptor interaction, and focal adhesion [39].…”

Section: Hoxd11mentioning

confidence: 99%

A new machine learning method for cancer mutation analysis

Habibi

Taheri

2022

Preprint

View full text Add to dashboard Cite

It is complicated to identify cancer-causing mutations. The recurrence of a mutation in patients remains one of the most reliable features of mutation driver status. However, some mutations are more likely to happen than others for various reasons. Different sequencing analysis has revealed that cancer driver genes operate across complex pathways and networks, with mutations often arising in a mutually exclusive pattern. Genes with low-frequency mutations are understudied as cancer-related genes, especially in the context of networks. Here we propose a machine learning method to study the functionality of mutually exclusive genes in the networks derived from mutation associations, gene-gene interactions, and graph clustering. These networks have indicated critical biological components in the essential pathways, especially those mutated at low frequency. Studying the network and not just the impact of a single gene significantly increases the statistical power of clinical analysis. The proposed method identified important driver genes with different frequencies. We studied the function and the associated pathways in which the candidate driver genes participate. By introducing lower-frequency genes, we recognized less studied cancer-related pathways. We also proposed a novel clustering method to specify driver modules in each type of cancer. We evaluated each cluster with different criteria, including the terms of biological processes and the number of simultaneous mutations in each cancer. Materials and implementations are available at: https://github.com/MahnazHabibi/Mutation_Analysis

show abstract

“…Homeobox (HOX) gene clusters encode a series of highly conserved transcription factors that are essential for tumorigenesis by regulating cell differentiation, angiogenesis and metastasis [ 15 , 16 ]. The dysregulation of HOX genes was associated with numerous solid malignancies and leukemia, suggesting its prominent roles in tumor progression [ 15 – 20 ]. However, the expression pattern of HOX clusters and their oncogenic roles remain unknown in PSCC.…”

Section: Introductionmentioning

confidence: 99%

“…Kristina et al reported that knockdown of the expression of HOXD11 repressed tumor growth and lung metastasis in Ewing’s sarcoma [ 19 ]. In addition, the overexpression of HOXD11 was a poor prognostic biomarker in head and neck squamous cell carcinoma and gliomas by promoting tumor proliferation and invasion [ 17 , 20 ]. Our results first revealed a significant association between HOXD11 expression and clinicopathological features as well as poor outcomes in a large PSCC cohort.…”

Section: Introductionmentioning

confidence: 99%

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

et al. 2022

View full text Add to dashboard Cite

The presence and extent of regional lymph node and distant metastasis are the most fatal prognostic factors in penile squamous cell carcinoma (PSCC). However, the available biomarkers and detailed mechanisms underlying the metastasis of PSCC remain elusive. Here, we explored the expression landscape of HOX genes in twelve paired PSCC tissues, including primary tumors, metastatic lymph nodes and corresponding normal tissues, and highlighted that HOXD11 was indispensable in the progression of PSCC. HOXD11 was upregulated in PSCC cell lines and tumors, especially in metastatic lymph nodes. High HOXD11 expression was associated with aggressive features, such as advanced pN stages, extranodal extension, pelvic lymph node and distant metastasis, and predicted poor survival. Furthermore, tumorigenesis assays demonstrated that knockdown of HOXD11 not only inhibited the capability of cell proliferation, invasion and tumor growth but also reduced the burden of metastatic lymph nodes. Further mechanistic studies indicated that miR-138-5p was a tumor suppressor in PSCC by inhibiting the translation of HOXD11 post-transcriptionally through binding to the 3′ untranslated region. Furthermore, HOXD11 activated the transcription of FN1 to decompose the extracellular matrix and to promote epithelial mesenchymal transition-like phenotype metastasis via FN1/MMP2/MMP9 pathways. Our study revealed that HOXD11 is a promising prognostic biomarker and predicts advanced disease with poor outcomes, which could serve as a potential therapeutic target for PSCC.

show abstract

Abnormal expression of HOXD11 promotes the malignant behavior of glioma cells and leads to poor prognosis of glioma patients

Cited by 10 publications

References 34 publications

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

A new machine learning method for cancer mutation analysis

miR-138-5p-mediated HOXD11 promotes cell invasion and metastasis by activating the FN1/MMP2/MMP9 pathway and predicts poor prognosis in penile squamous cell carcinoma

Contact Info

Product

Resources

About