MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma through a Sox9-Mediated Positive Feedback Loop

Chen, Yanyan; Wang, Bin; Huang, Mengxi; Wang, Tao; Hu, Chao; Liu, Qin; Han, Dong Cho; Chen, Cheng; Zhang, Junliang; Li, Zhiping; Liu, Chao; Lei, Wenbin; Chang, Yue; Mei-juan, WU; Xiang, Dan; Chen, Yitian; Wang, Rui; Wei-qian, Huang; Lei, Zengjie; Chen, Xiaoyuan

doi:10.1158/0008-5472.can-19-1764

Cited by 37 publications

(38 citation statements)

References 40 publications

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“…Currently, the association of SOX10 [52] , MDM4 [53] , MAPK8 [54] , MDM2 [55] , CDK4 [56] , CCND3 [57] , Runx2 [58] , Gli1 [59] , FRS2 mutation [55] with osteosarcoma formation has been documented, while no report is so far available concerning GPC3 mutation and expression in osteosarcomas especially those with metastasis and/or multidrug resistance. It has been found that GPC3 is an oncofetal protein expressed in 72% of hepatocellular carcinomas [60] and 97% in hepatoblastomas [59] .…”

Section: Discussionmentioning

confidence: 99%

Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target

Nie

Yang

Li³

et al. 2021

Journal of Bone Oncology

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Section: Discussionmentioning

confidence: 99%

Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target

Nie

Yang

Li³

et al. 2021

Journal of Bone Oncology

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“…Inhibition of MAFB expression in ovarian cancer cells inhibited their proliferation and invasion capacities, similar to that observed after RecQL4 suppression. Recent evidence points out a role of MAFB in osteosarcoma by promoting cancer stemness and tumor aggressiveness [Chen et al, 2020]. It is likely that RecQL4 exerts its effect on cancer stemness through a positive regulation of MAFB.…”

Section: Recql4 Protects Cancer Cells From Endogenous and Exogenous Dna Damagementioning

confidence: 99%

“…Previous studies provided experimental evidence for the indirect roles of RecQL4 in cancer cell invasion and metastasis [Chen et al, 2020;Guo et al, 2020;Lu et al, 2020;Machlowska et al, 2020]. Su et al [2010] provided the first evidence that RecQL4 suppression reduced the human prostate cancer cell invasion in vitro and tumor growth of mouse xenografts in vivo.…”

Section: Recql4 Contributes To Cancer Cell Survival Invasion and Metastasismentioning

confidence: 99%

“…Guo et al [2020] showed that the transcription factor MAFB is a direct downstream target of RecQL4, and MAFB expression is tightly coupled to RecQL4 expression. Strikingly, suppression of MAFB abolishes the proliferation and invasion capacities of ovarian cancer cells, and MAFB is demonstrated to potentiate stemness in osteosarcoma [Chen et al, 2020]. RecQL4 was shown to be essential for hematopoietic stem cells in mice, and RecQL4-deficient stems cells were not transplantable [Smeets et al, 2014].…”

Section: Recql4 Is a Molecular Target For Cancer Therapymentioning

confidence: 99%

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Human RecQL4 as a Novel Molecular Target for Cancer Therapy

Balajee¹

2021

Cytogenet Genome Res

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Human RecQ helicases play diverse roles in the maintenance of genomic stability. Inactivating mutations in 3 of the 5 human RecQ helicases are responsible for the pathogenesis of Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). WS, BS, and RTS patients are at increased risk for developing many age-associated diseases including cancer. Mutations in RecQL1 and RecQL5 have not yet been associated with any human diseases so far. In terms of disease outcome, RecQL4 deserves special attention because mutations in RecQL4 result in 3 autosomal recessive syndromes (RTS type II, RAPADILINO, and BGS). RecQL4, like other human RecQ helicases, has been demonstrated to play a crucial role in the maintenance of genomic stability through participation in diverse DNA metabolic activities. Increased incidence of osteosarcoma in RecQL4-mutated RTS patients and elevated expression of RecQL4 in sporadic cancers including osteosarcoma suggest that loss or gain of RecQL4 expression is linked with cancer susceptibility. In this review, current and future perspectives are discussed on the potential use of RecQL4 as a novel cancer therapeutic target.

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“…The MAF TFs regulate gene expression and differentiation in a wide variety of tissues and are also involved in human diseases, including tumorigenesis (17,18). There are five MAF TFs in human cells: MAFA, MAFB, MAFF, MAFG, and MAFK.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF

Chen¹,

Lu²,

Huang³

et al. 2021

Journal of Clinical Investigation

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BackgroundLiver tumor-initiating cells (TICs) are involved in liver tumorigenesis, metastasis, drug resistance and relapse, but the regulatory mechanisms of liver TICs are largely unknown. Here, we have identified a functional circular RNA, termed circRNA activating MAFF (cia-MAF), that is robustly expressed in liver cancer and liver TICs. cia-MAF knockout primary cells and cia-maf knockout liver tumors harbor decreased ratios of TICs, and display impaired liver tumorigenesis, self-renewal and metastatic capacities. In contrast, cia-MAF overexpression drives liver TIC propagation, self-renewal and metastasis. Mechanistically, cia-MAF binds to the MAFF promoter, recruits the TIP60 complex to the MAFF promoter, and finally promotes MAFF expression. Loss of cia-MAF function attenuates the combination between the TIP60 complex and the MAFF promoter.MAFF is highly expressed in liver tumors and liver TICs, and its antisense oligo (ASO) has therapeutic potential in treating liver cancer without MAFA/MAFG gene copy number alterations (CNAs). This study reveal an additional layer for liver TIC regulation as well as circRNA function, and also provide an additional target for eliminating liver TICs, especially for liver tumor without MAFA/MAFG gene CNAs.

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MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma through a Sox9-Mediated Positive Feedback Loop

Abstract: Transcription factors MAFB and Sox9 form a positive feedback loop to maintain cell stemness and tumor growth in vitro and in vivo, revealing a potential target pathway for therapeutic intervention in osteosarcoma.. Research.

Cited by 37 publications

References 40 publications

Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target

Identification of GPC3 mutation and upregulation in a multidrug resistant osteosarcoma and its spheroids as therapeutic target

Human RecQL4 as a Novel Molecular Target for Cancer Therapy

Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF

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