ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

He, Yuhao; Yeh, Ming-Hsin; Chen, Hsiao-Fan; Wang, Tsu-Shing; Wong, Ruey-Hong; Wei, Yue; Huynh, Thanh Kieu; Hu, Dai-Wei; Cheng, Fang-Ju; Chen, Jhen-Yu; Hu, Shu-Wei; Huang, Chien-Hua; Chen, Yeh; Yu, Jiaxin; Cheng, Wei‐Chung; Shen, Po-Chien; Liu, Liang‐Chih; Huang, Chih‐Hao; Chang, Ya‐Jen; Huang, Wei-Chien

doi:10.1016/j.omtn.2021.07.022

Cited by 14 publications

(6 citation statements)

References 67 publications

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“…However, DDB2 is reported to have dual functions in cancer, sometimes with tumor suppressive properties and sometimes functioning as an oncogene ( 34 ). In cancer cells, DDB2 may also promote the repair of cancer DNA lesions induced by radiation or chemotherapy leading to chemo/radioresistance ( 34 – 36 ) ( 11 ). The transcription factor p53 plays critical roles in the suppression of tumor development, and MDM2 is the primary negative regulatory factor of p53 ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma

Han

Min²,

Noh³

et al. 2022

Front. Oncol.

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Glioblastoma multiforme (GBM) is the most malignant brain tumor with an extremely poor prognosis. The Cancer Genome Atlas (TCGA) database has been used to confirm the roles played by 10 canonical oncogenic signaling pathways in various cancers. The purpose of this study was to evaluate the expression of genes in these 10 canonical oncogenic signaling pathways, which are significantly related to mortality and disease progression in GBM patients. Clinicopathological information and mRNA expression data of 525 patients with GBM were obtained from TCGA database. Gene sets related to the 10 oncogenic signaling pathways were investigated via Gene Set Enrichment Analysis. Multivariate Cox regression analysis was performed for all the genes significantly associated with mortality and disease progression for each oncogenic signaling pathway in GBM patients. We found 12 independent genes from the 10 oncogenic signaling pathways that were significantly related to mortality and disease progression in GBM patients. Considering the roles of these 12 significant genes in cancer, we suggest possible mechanisms affecting the prognosis of GBM. We also observed that the expression of 6 of the genes significantly associated with a poor prognosis of GBM, showed negative correlations with CD8+ T-cells in GBM tissue. Using a large-scale open database, we identified 12 genes belonging to 10 well-known oncogenic canonical pathways, which were significantly associated with mortality and disease progression in patients with GBM. We believe that our findings will contribute to a better understanding of the mechanisms underlying the pathophysiology of GBM in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma

Han

Min²,

Noh³

et al. 2022

Front. Oncol.

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“…LincRNA-p21 , also called p53 pathway corepressor 1 protein tumor ( TRP53COR1 ), is associated with VDR signaling [ 80 ]. It was shown that its expression was induced by chemotherapy and mediated by a mutated p53 form that targeted the G quadruplex structure rather than the p53 response elements in its promoter [ 91 ]. It was shown that lincRNA-p21 was upregulated in 4T1 breast tumor-associated macrophages (TAMs) [ 92 ].…”

Section: Long Noncoding Rnas and Vitamin D Signaling In Breast Cancermentioning

confidence: 99%

Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling

Błasiak

Chojnacki

Pawłowska

et al. 2022

IJMS

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Dietary vitamin D3 has attracted wide interest as a natural compound for breast cancer prevention and therapy, supported by in vitro and animal studies. The exact mechanism of such action of vitamin D3 is unknown and may include several independent or partly dependent pathways. The active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D, calcitriol), binds to the vitamin D receptor (VDR) and induces its translocation to the nucleus, where it transactivates a myriad of genes. Vitamin D3 is involved in the maintenance of a normal epigenetic profile whose disturbance may contribute to breast cancer. In general, the protective effect of vitamin D3 against breast cancer is underlined by inhibition of proliferation and migration, stimulation of differentiation and apoptosis, and inhibition of epithelial/mesenchymal transition in breast cells. Vitamin D3 may also inhibit the transformation of normal mammary progenitors into breast cancer stem cells that initiate and sustain the growth of breast tumors. As long noncoding RNAs (lncRNAs) play an important role in breast cancer pathogenesis, and the specific mechanisms underlying this role are poorly understood, we provided several arguments that vitamin D3/VDR may induce protective effects in breast cancer through modulation of lncRNAs that are important for breast cancer pathogenesis. The main lncRNAs candidates to mediate the protective effect of vitamin D3 in breast cancer are lncBCAS1-4_1, AFAP1 antisense RNA 1 (AFAP1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein-coding RNA 511 (LINC00511), LINC00346, small nucleolar RNA host gene 6 (SNHG6), and SNHG16, but there is a rationale to explore several other lncRNAs.

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“…Another article also reported that wild-type p53 can bind to G-quadruplexes on MYC promoter to repress MYC expression [ 80 ]. Both wild-type and non-gain-of-function p53 mutants can activate lincRNA-p21 through binding to G-quadruplexes on lincRNA-p21 promoter [ 81 ], and lincRNA-p21 can repress STAT3 [ 82 ]. STAT3 can bind to the HSP70 promoter to active HSP70 expression [ 83 , 84 ].…”

Section: Factors Influencing P53 Mutant Gain Of Functionmentioning

confidence: 99%

P63 and P73 Activation in Cancers with p53 Mutation

et al. 2022

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The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

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ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

Cited by 14 publications

References 67 publications

Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma

Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma

Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling

P63 and P73 Activation in Cancers with p53 Mutation

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