HOXA1 promotes proliferation and metastasis of bladder cancer by enhancing SMAD3 transcription

Chen, Shuangchen; Ge, Shen; Wang, Guanqun; Ye, Jing; Xu, Jun; Huang, Chunxia; Yang, Shangqi

doi:10.1016/j.prp.2022.154141

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…Several assessments employing microarray and RNA-seq data have been performed to uncover novel therapeutic targets and biomarkers for BC; however, inconsistencies exist on the DEGs detected in various studies. [ 21 , 22 ] Of interest, we present the first report to the use of RRA-WGCNA to explore novel hub genes related to BLCA.…”

Section: Discussionmentioning

confidence: 99%

Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses

Feng

Zhong²,

Jian-hua³

et al. 2022

Medicine

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Background: Bladder cancer (BC) is among the most frequent cancers globally. Although substantial efforts have been put to understand its pathogenesis, its underlying molecular mechanisms have not been fully elucidated. Methods: The robust rank aggregation approach was adopted to integrate 4 eligible bladder urothelial carcinoma microarray datasets from the Gene Expression Omnibus. Differentially expressed gene sets were identified between tumor samples and equivalent healthy samples. We constructed gene co-expression networks using weighted gene co-expression network to explore the alleged relationship between BC clinical characteristics and gene sets, as well as to identify hub genes. We also incorporated the weighted gene co-expression network and robust rank aggregation to screen differentially expressed genes. Results: CDH11, COL6A3, EDNRA, and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, receiver operating characteristics curves and Kaplan–Meier plots showed that the genes exhibited favorable diagnostic and prognostic value for BC. Based on gene set enrichment analysis for single hub gene, all the genes were closely linked to BC cell proliferation. Conclusions: These results offer unique insight into the pathogenesis of BC and recognize CDH11, COL6A3, EDNRA, and SERPINF1 as potential biomarkers with diagnostic and prognostic roles in BC.

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Section: Discussionmentioning

confidence: 99%

Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses

Feng

Zhong²,

Jian-hua³

et al. 2022

Medicine

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“…HOXA1 is mainly known to be involved in cell differentiation, growth, apoptosis, metastasis, and regulation of embryonic development. Dysregulation of this gene primarily involves tumor development in oral, melanoma, gastric, and bladder cancers ( Chen et al, 2022 ). Figure 3 shows the major genes upregulated/downregulated by RA gene activation.…”

Section: Retinoic Acid and Its Signaling Mechanismmentioning

confidence: 99%

Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers

Lavudi,

Nuguri,

Olverson

et al. 2023

Front. Cell Dev. Biol.

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Retinoic acid (RA) is a vital metabolite derived from vitamin A. RA plays a prominent role during development, which helps in embryological advancement and cellular differentiation. Mechanistically, RA binds to its definite nuclear receptors including the retinoic acid receptor and retinoid X receptor, thus triggering gene transcription and further consequences in gene regulation. This functional heterodimer activation later results in gene activation/inactivation. Several reports have been published related to the detailed embryonic and developmental role of retinoic acids and as an anti-cancer drug for specific cancers, including acute promyelocytic leukemia, breast cancer, and prostate cancer. Nonetheless, the other side of all-trans retinoic acid (ATRA) has not been explored widely yet. In this review, we focused on the role of the RA pathway and its downstream gene activation in relation to cancer progression. Furthermore, we explored the ways of targeting the retinoic acid pathway by focusing on the dual role of aldehyde dehydrogenase (ALDH) family enzymes. Combination strategies by combining RA targets with ALDH-specific targets make the tumor cells sensitive to the treatment and improve the progression-free survival of the patients. In addition to the genomic effects of ATRA, we also highlighted the role of ATRA in non-canonical mechanisms as an immune checkpoint inhibitor, thus targeting the immune oncological perspective of cancer treatments in the current era. The role of ATRA in activating independent mechanisms is also explained in this review. This review also highlights the current clinical trials of ATRA in combination with other chemotherapeutic drugs and explains the future directional insights related to ATRA usage.

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“…In the context of cancer research, upregulation of HOXA1 has been observed in BC. Increased expression of HOXA1 has been shown to promote cell proliferation and enhance metastasis by directly binding to the promoter region of SMAD3, thus regulating its transcription [ 192 ]. Furthermore, HOXA1 has the ability to facilitate the enrichment of H3K4me1 and H3K27ac in the enhancer region of MEIS3, resulting in enhanced expression of MEIS3.…”

Section: Introductionmentioning

confidence: 99%

Role of HOXA1-4 in the development of genetic and malignant diseases

Wang,

Sun,

Cao

et al. 2024

Biomark Res

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The HOXA genes, belonging to the HOX family, encompass 11 members (HOXA1-11) and exert critical functions in early embryonic development, as well as various adult processes. Furthermore, dysregulation of HOXA genes is implicated in genetic diseases, heart disease, and various cancers. In this comprehensive overview, we primarily focused on the HOXA1-4 genes and their associated functions and diseases. Emphasis was placed on elucidating the impact of abnormal expression of these genes and highlighting their significance in maintaining optimal health and their involvement in the development of genetic and malignant diseases. Furthermore, we delved into their regulatory mechanisms, functional roles, and underlying biology and explored the therapeutic potential of targeting HOXA1-4 genes for the treatment of malignancies. Additionally, we explored the utility of HOXA1-4 genes as biomarkers for monitoring cancer recurrence and metastasis.

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HOXA1 promotes proliferation and metastasis of bladder cancer by enhancing SMAD3 transcription

Cited by 9 publications

References 54 publications

Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses

Identifying stage-associated hub genes in bladder cancer via weighted gene co-expression network and robust rank aggregation analyses

Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers

Role of HOXA1-4 in the development of genetic and malignant diseases

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