Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HO...Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HOXC6 sig-nificantly inhibits BLCA cell proliferation,migration and invasion,induces apo-ptosis and arrests the cell cycle at G0/G1.In addition,HOXC6 also regulates pa-thways related to chemical carcinogenesis and reactive oxygen species,with a strong association with the target gene TIMELESS,supported by binding signals in its promoter region.Here,we discuss the role of HOXC6 as a potential bio-marker and therapeutic target,contributing to a deeper understanding of the HOXC6-TIMELESS axis and its implications for advancing BLCA research and therapy.展开更多
Background:A keloid is a disease of excessive fibrosis that is characterized by the aberrant prolifer-ation of fibroblasts.However,the molecular mechanisms of fibroblasts during the development of keloids remain uncle...Background:A keloid is a disease of excessive fibrosis that is characterized by the aberrant prolifer-ation of fibroblasts.However,the molecular mechanisms of fibroblasts during the development of keloids remain unclear.This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts,providing new ideas for the prevention and treatment of keloids.Methods:We utilized bioinformatics tools to analyze data from keloid fibroblasts(KFs)available in the Gene Expression Omnibus(GEO)database to identify the key genes involved in keloid development.Homeobox C6(HOXC6)emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction,western blot(WB)and immunohistochemistry.Subsequently,the effects of down-regulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8,flow cytometry,transwell migration and WB assays.Meanwhile,we performed transcriptome sequencing and gene set enrichment analysis(GSEA)to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments.Results:HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs.Downregulation of HOXC6 inhibited proliferation,migration and extracellular matrix(ECM)accumulation and promoted KF apoptosis.GSEA pre-dicted that the hypoxia signaling pathway was associated with HOXC6 in KFs.Transcriptome sequencing suggested that the extracellular regulated protein kinase(ERK)pathway was one of the downstream pathways of HOXC6 in KFs.Our experiments confirmed that hypoxia-inducible factor-1α(HIF-1α)upregulates HOXC6,contributing to KFs proliferation,migration,apoptosis inhibition and collagen accumulation through the ERK signaling pathway.Conclusions:Our findings first revealed that HOXC6 acts as an oncogenic driver in the molec-ular mechanisms of fibroblasts in keloids.The HIF-1α/HOXC6/ERK axis promotes proliferation,migration and ECM production by KFs,contributing to the progression of keloids.Taken together,HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.展开更多
基金Supported by National Key R&D Program of China,No.2023YFC2507904Hubei Strategic Science and Technology Talent Plan,No.2024DJA037+1 种基金National Natural Science Foundation of China,No.32270768,No.82273970 and No.82370715Innovation Group Project of Hubei Province No.2023AFA026.
文摘Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HOXC6 sig-nificantly inhibits BLCA cell proliferation,migration and invasion,induces apo-ptosis and arrests the cell cycle at G0/G1.In addition,HOXC6 also regulates pa-thways related to chemical carcinogenesis and reactive oxygen species,with a strong association with the target gene TIMELESS,supported by binding signals in its promoter region.Here,we discuss the role of HOXC6 as a potential bio-marker and therapeutic target,contributing to a deeper understanding of the HOXC6-TIMELESS axis and its implications for advancing BLCA research and therapy.
基金supported by the National Natural Science Foundation of China(grant numbers 81703098 and 82073464)the President Foundation of Nanfang Hospital,Southern Medical University(grant numbers 2021B004 and 2021L002).
文摘Background:A keloid is a disease of excessive fibrosis that is characterized by the aberrant prolifer-ation of fibroblasts.However,the molecular mechanisms of fibroblasts during the development of keloids remain unclear.This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts,providing new ideas for the prevention and treatment of keloids.Methods:We utilized bioinformatics tools to analyze data from keloid fibroblasts(KFs)available in the Gene Expression Omnibus(GEO)database to identify the key genes involved in keloid development.Homeobox C6(HOXC6)emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction,western blot(WB)and immunohistochemistry.Subsequently,the effects of down-regulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8,flow cytometry,transwell migration and WB assays.Meanwhile,we performed transcriptome sequencing and gene set enrichment analysis(GSEA)to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments.Results:HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs.Downregulation of HOXC6 inhibited proliferation,migration and extracellular matrix(ECM)accumulation and promoted KF apoptosis.GSEA pre-dicted that the hypoxia signaling pathway was associated with HOXC6 in KFs.Transcriptome sequencing suggested that the extracellular regulated protein kinase(ERK)pathway was one of the downstream pathways of HOXC6 in KFs.Our experiments confirmed that hypoxia-inducible factor-1α(HIF-1α)upregulates HOXC6,contributing to KFs proliferation,migration,apoptosis inhibition and collagen accumulation through the ERK signaling pathway.Conclusions:Our findings first revealed that HOXC6 acts as an oncogenic driver in the molec-ular mechanisms of fibroblasts in keloids.The HIF-1α/HOXC6/ERK axis promotes proliferation,migration and ECM production by KFs,contributing to the progression of keloids.Taken together,HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.
